Clinical Hemorheology and Microcirculation - Volume Pre-press, issue Pre-press

Authors: Teng, Yanling | Ren, Fei | Wang, Yanan | Xu, Hua | Song, Hejian

Article Type: Research Article

Abstract: BACKGROUND: Previous data have shown that circ_0033596 is involved in the pathogenesis of atherosclerosis (AS). The study aims to reveal the detailed mechanism of circ_0033596 in AS. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish an AS cell model. Quantitative real-time polymerase chain reaction and western blot were implemented to detect the expression of circ_0033596, miR-637, growth factor receptor bound protein2 (GRB2), BCL2-associated x protein (Bax) and B-cell lymphoma-2 (Bcl-2). Cell viability, proliferation, apoptosis and tube formation were investigated by cell counting kit-8, EdU assay, flow cytometry and tube formation …assay, respectively. The production of interleukin (IL-6) and tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay. Oxidative stress was evaluated by lipid peroxidation malondialdehyde assay kit and superoxide dismutase activity assay kit. Dual-luciferase reporter assay, RNA pull-down assay and RIP assay were performed to identify the associations among circ_0033596, miR-637 and GRB2. RESULTS: The expression of circ_0033596 and GRB2 was significantly increased, while miR-637 was decreased in the blood of AS patients and ox-LDL-induced HUVECs compared with controls. Ox-LDL treatment inhibited HUVEC viability, proliferation and angiogenic ability and induced cell apoptosis, inflammation and oxidative stress, while these effects were attenuated after circ_0033596 knockdown. Circ_0033596 interacted with miR-637 and regulated ox-LDL-induced HUVEC damage by targeting miR-637. In addition, GRB2, a target gene of miR-637, participated in ox-LDL-induced HUVEC injury by combining with miR-637. Importantly, circ_0033596 activated GRB2 by interacting with miR-637. CONCLUSION: Circ_0033596 depletion protected against ox-LDL-induced HUVEC injury by miR-637/GRB2 pathway, providing a therapeutic target for AS. Show more

Keywords: AS, circ_0033596, miR-637, GRB2

DOI: 10.3233/CH-221686

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2023

Authors: Binneboessel, Stephan | Masyuk, Maryna | Piayda, Kerstin | Bruno, Raphael Romano | Wernly, Bernhard | Jirak, Peter | Wolff, Georg | Gerdes, Norbert | Baldia, Philipp Heinrich | Kelm, Malte | Nienhaus, Fabian | Lang, Alexander | Winkels, Holger | Geerling, Gerd | Guthoff, Rainer | Kaya, Sema | Flossmann, Gerald | Riemer, Thomas | Baertschi, Michael | Jung, Christian

Article Type: Research Article

Abstract: BACKGROUND: “Spaceflight associated neuro-ocular syndrome” (SANS) represents a challenging health condition in modern space medicine. Forty-eight percent of astronauts are diagnosed with SANS after long-term space missions. The pathophysiological mechanism seems to be multifactorial, and yet remains unknown. In this proof-of-concept study we plan to investigate retinal microcirculatory changes in weightlessness and aim to identify their role in the development of SANS. METHODS AND DESIGN: Healthy individuals will take part in a parabolic flight campaign, which recreates fractioned total weightlessness periods. The airplane is specifically equipped, and designed for the execution of parabolic flight maneuvers and scientific research …in microgravity. Retinal microcirculation will be assessed with a modified fundus camera, which allows dynamic vessel analysis. We will additionally measure intra-ocular pressure and hemodynamic changes during each phase of the flight. Blood samples will be analyzed at baseline, one hour and 24 hours after exposure to weightlessness. CONCLUSIONS: This pilot study aims to investigate the feasibility of retinal microcirculation assessment during varying gravity. Results of this study may generate insights whether venous stasis in the eye, surrogated by the dilatation of retinal vessels and increase in intraocular pressure as signs of venous insufficiency, may potentially contribute to the development of SANS. Show more

Keywords: Microgravity, parabolic flight campaign, retinal microcirculation, dynamic vessel analyzer, spaceflight associated neuro-ocular syndrome

DOI: 10.3233/CH-221691

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2023

Authors: Hojker, Marta | Tršan, Jure | Tršan, Uroš | Gale, Ana | Jerman, Alexander | Košuta, Daniel

Article Type: Research Article

Abstract: BACKGROUND: The predictive value of coagulation markers for venous thromboembolism (VTE) in Covid-19 patients has been investigated with conflicting results. OBJECTIVE: Our aim was to investigate the correlation between biomarkers and VTE and the predictive value of D-dimer for VTE in hospitalized Covid-19 patients. METHODS: Complete blood count, inflammatory and coagulation biomarkers at admission were collected. VTE was defined as diagnosed pulmonary embolism or deep vein thrombosis. Events were defined as in-hospital death or ICU admission. Predictors of VTE were identified with Pearson prediction models. A ROC curve was constructed to assess the predictive value of …D-dimer. RESULTS: 1651 participants were included, 111 VTE were identified. Events incidence was higher in the VTE group (49.5% vs 28.2%, p  <  0.001). Neutrophil-lymphocyte ratio (NLR, 0.001; 95% CI 0.000–0.002; p 0.019) and D-dimer (0.00005; 95% CI 0.00002–0.00008; p  <  0.001), Geneva score (0.026; 95% CI 0.012–0.040; p  <  0.001) and Wells score (0.047; 95% CI 0.033–0.061; p  <  0.001) were associated with VTE. D-dimer had a goor predictive value for VTE (ROC area 0.85, 95% CI 0.816–0.893), with an optimal cut-off value of 2677μg/L (Youden index of 0,602). CONCLUSIONS: Among coagulation biomarkers D-dimer had the best predictive value for VTE, but higher cut-off values should be used in Covid-19. Show more

Keywords: D-dimer, venous thromboembolism, Covid-19, neutrophil-lymphocyte ratio, inflammatory biomarkers, coagulation biomarkers

DOI: 10.3233/CH-221664

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Caimi, G. | Carlisi, M.

Article Type: Research Article

Abstract: According to Wells classification, it is possible to distinguish the primary hyperviscosity syndromes in polycythemic, sclerocythemic and sieric and/or plasmatic. In polycythemia vera, multiple myeloma, Waldenström’s macroglobulinemia, and monoclonal gammopathy of undetermined significance, we have observed an unexpected behaviour of the erythrocyte deformability. This data highlights that the hemorheological alteration present in polycythemia vera has not been related to the increase of RBC mass only, as well as that present in plasmacellular dyscrasias has not been attributable to the increase of plasma viscosity only. The aim of this paper is to suggest some starting points for an accurate reflection, …emphasizing the need of a revision of the current classification of primary hyperviscosity syndromes. Show more

Keywords: Erythrocyte deformability, primary hyperviscosity syndromes, polycythemia vera, multiple myeloma, Waldenström’s macroglobulinemia, monoclonal gammopathy of undetermined significance

DOI: 10.3233/CH-221549

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2023

Authors: Lehmann, Christian | Zhou, Juan

Article Type: Research Article

Abstract: Cannabinoids play critical roles in human pathophysiology through the cannabinoid (CB) receptors and non-CB receptors on variety of cells, tissues, and organs. Microvasculature with the inside bloodstream containing the plasmatic and cellular components exerts multiple functions in maintaining tissue and organ physiology through microcirculation. This review focusses on the impact of cannabinoids on the microvasculature, including mechanisms mediated by both CB receptor-related pathways and CB receptor-independent pathways.

Keywords: Cannabinoids, microcirculation, cannabinoid receptors, smooth muscle cells

DOI: 10.3233/CH-221677

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2022

Authors: Binneboessel, Stephan | Bruno, Raphael Romano | Wernly, Bernhard | Masyuk, Maryna | Flaatten, Hans | Fjølner, Jesper | Wolff, Georg | Kelm, Malte | Beil, Michael | Sviri, Sigal | Szczeklik, Wojciech | Leaver, Susannah | De Lange, Dylan W. | Guidet, Bertrand | Jung, Christian

Article Type: Research Article

Abstract: BACKGROUND: COVID-19 is associated with cytokine release in critical disease states. Thus, cytokine absorption has been proposed as a therapeutic option. This study investigated the influence of cytokine absorption on mortality in old critical patients with COVID-19 and renal failure admitted to intensive care units (ICU). METHODS: This retrospective analysis of a prospective international observation study (the COVIP study) analysed ICU patients≥70 years with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, clinical frailty scale (CFS), ICU therapy details including renal replacement therapy (RRT) with/without cytokine absorption were collected. The cytokine absorption group was compared to patients …receiving RRT without cytokine absorption RESULTS: Among 3927 patients, 503 received RRT; among them 47 patients were treated with cytokine absorption. Mortality rates were high in both groups with increased rates in the cytokine group for ICU mortality and 30-day mortality, but not for 3-month mortality. Logistic regression analysis indicated that SOFA-score, but not cytokine absorption was associated with mortality. CONCLUSIONS: Critical COVID-19 patients with renal failure treated with cytokine absorption showed higher short term mortality rates when compared to patients with renal replacement therapy alone. Mortality is associated with disease severity, but not cytokine absorption in a multivariate analysis. Show more

Keywords: Cytokine absorption, COVID-19, critically ill, ICU, mortality, srenal replacement therapy

DOI: 10.3233/CH-221579

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Li, Chunxiao | Zhang, Huili | Chen, Jing | Shao, Sihui | Li, Xin | Yao, Minghua | Zheng, Yi | Wu, Rong | Shi, Jun

Article Type: Research Article

Abstract: OBJECTIVES: The purpose of our study is to present a method combining radiomics with deep learning and clinical data for improved differential diagnosis of sclerosing adenosis (SA)and breast cancer (BC). METHODS: A total of 97 patients with SA and 100 patients with BC were included in this study. The best model for classification was selected from among four different convolutional neural network (CNN) models, including Vgg16, Resnet18, Resnet50, and Desenet121. The intra-/inter-class correlation coefficient and least absolute shrinkage and selection operator method were used for radiomics feature selection. The clinical features selected were patient age and nodule size. …The overall accuracy, sensitivity, specificity, Youden index, positive predictive value, negative predictive value, and area under curve (AUC) value were calculated for comparison of diagnostic efficacy. RESULTS: All the CNN models combined with radiomics and clinical data were significantly superior to CNN models only. The Desenet121+radiomics+clinical data model showed the best classification performance with an accuracy of 86.80%, sensitivity of 87.60%, specificity of 86.20% and AUC of 0.915, which was better than that of the CNN model only, which had an accuracy of 85.23%, sensitivity of 85.48%, specificity of 85.02%, and AUC of 0.870. In comparison, the diagnostic accuracy, sensitivity, specificity, and AUC value for breast radiologists were 72.08%, 100%, 43.30%, and 0.716, respectively. CONCLUSIONS: A combination of the CNN-radiomics model and clinical data could be a helpful auxiliary diagnostic tool for distinguishing between SA and BC. Show more

Keywords: Deep learning, radiomics, breast cancer, sclerosing adenosis

DOI: 10.3233/CH-221608

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Watson, Oliver | Zaldua, Jun-Cezar | Pillai, Suresh | Whitley, Janet | Howard, Matthew | Lawrence, Matthew | Hawkins, Karl | Morris, Keith | Evans, Phillip Adrian

Article Type: Research Article

Abstract: BACKGROUND: A significant degree of mortality and morbidity in Covid-19 is through thromboembolic complications, only partially mitigated by anticoagulant therapy. Reliable markers of infection severity are not fully established. OBJECTIVES: This study investigated whether visco-elastic biomarkers predict disease severity on presentation to the Emergency Department (ED) and how they measure response to anticoagulation METHODS: Patients testing positive for Covid-19 at a large University Teaching Hospital ED were recruited at presentation. Multiple blood samples were taken throughout hospital admission to monitor disease progression with end outcome recorded. Visco-elastic markers, fractal dimension (d f ) and Time …to Gel Point (TGP) which measure the properties of the incipient clot were compared in patients with and without anticoagulation by Low Molecular Weight Heparin (LMWH). RESULTS: TGP and d f did not predict severity of infection with Covid-19. Although LMWH prolonged TGP, there was no change in d f indicating LMWH did not change clot microstructure. CONCLUSIONS: Therapeutic efficacy of LMWH appears blunted in Covid-19 infection. This may be due to the inflammatory state creating a resistance to LMWH activity, which may explain why LMWH appears less effective in Covid-19 compared to other disease states. Covid-19 was not predicted by visco-elastic testing at the time of ED presentation. Show more

Keywords: Covid-19, coagulopathy, visco-elastic testing, anticoagulation, Heparin resistance

DOI: 10.3233/CH-221635

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Kaiser, Ulrich | Dropco, Ivor | Reuthner, Kathrin | Ertl, Michael | Schlitt, Hans Jürgen | Herr, Wolfgang | Stroszczynski, Christian | Jung, Ernst Michael

Article Type: Research Article

Abstract: OBJECTIVE: The study aim was to investigate the use of a novel device, the Vscan Air™, for rapidly and effectively performing ultrasound in student teaching during the COVID-19 pandemic. MATERIAL AND METHODS: As part of the ultrasound practical course with integrated hands-on activity required by the regular medical curriculum, 100 medical students were instructed in the use of the Vscan Air™, including duplex mode. They then evaluated the quality of the ultrasound images obtained by the Vscan Air™ from previously selected organs. RESULTS: 100 students were interviewed (female n  = 68, male n  = 32; age >18 years …n  = 100). The rated image quality never fell below a mean of 3 for the examined organs and portal vein flow (liver 4,58; spleen 3,99; kidneys 4,29; aorta 4,16; Douglas/rectovesical space 4,14; portal vein 4,43; pancreas 3,53; Focused Assessment with Sonography for Trauma 4,38). Scores below 3 were found sporadically in ultrasounds of the spleen (n  = 4), kidneys (n  = 3), Douglas/rectovesical space (n  = 2), and pancreas (n  = 15). The liver was rated the lowest for 59 ratings. The portal vein was evaluated in 68 cases. The hepatic artery and hepatic veins could be also visualized in all 68 examinations. The aorta was evaluated in 62 cases. CONCLUSION: The Vscan Air™ technology offered adequate image quality and provided a new, fast and patient-oriented technique to support continuous ultrasound examinations and education of students, especially during a pandemic. Particularly noteworthy is the uncomplicated compliance with the required high level of hygiene. Show more

Keywords: VScan Air, mobile ultrasound, ultrasound, student teaching

DOI: 10.3233/CH-229104

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Anker, Alexandra M. | Lenhard, Jasmin | Klein, Silvan M. | Felthaus, Oliver | Prantl, Lukas | Ruewe, Marc

Article Type: Research Article

Abstract: BACKGROUND: Recent studies have demonstrated that local application of corticosteroids reduces wound exudation following abdominoplasty and other reconstructive surgical procedures. On the other hand, corticosteroids might provoke wound healing disturbances due to their immunosuppressive effects. OBJECTIVE: The main objective of this study was to gain further information about the impact of the corticosteroid triamcinolone on cell migration in abdominoplasty patients. METHODS: An in-vitro scratch assay wound healing model was applied to observe cell migration of fibroblasts cultured with nutrient medium containing human seroma aspirate±triamcinolone. RESULTS: There were no significant differences regarding cell migration …when fibroblasts were incubated with triamcinolone + seroma containing culture medium compared to seroma containing culture medium without triamcinolone. CONCLUSIONS: The performed in-vitro study suggests that triamcinolone does not decelerate fibroblast cell migration which is considered as a surrogate of wound healing. Show more

Keywords: Cell migration, fibroblasts, corticosteroids, triamcinolone, scratch assay

DOI: 10.3233/CH-229106

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2022