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

Authors: Farber, Paulo L. | Dias, Ana | Freitas, Teresa | Pinho, Ana C. | Viggiano, Diego | Saldanha, Carlota | Silva-Herdade, Ana S.

Article Type: Research Article

Abstract: Background: Calcium, vitamin D and insulin resistance are linked to osteoporosis and cardiovascular disease in menopause. Objective: Determine if hemorheological parameters related to blood viscosity in microcirculation are linked to calcium metabolism and insulin resistance in menopause. Methods: 25-Hydroxyvitamin D (25(OH)D)), 1, 25-dihydroxyvitamin D3 (1, 25(OH)2 D), Parathyroid Hormone, ionized calcium, Glucose, Insulin and Hemoglobin A1c were measured in blood from 43 volunteers. Red blood cells (RBC) aggregation, RBC deformability and Whole Blood Viscosity were also performed. Results: 25(OH)D showed a positive correlation with RBC deformability 0.60 Pa. Subjects with 25(OH)D≤29.00 ng/mL had lower RBC …deformability 0.60 Pa. and higher RBC Aggregation and higher HOMA-IR. Ionized calcium showed a negative correlation with RBC Aggregation. Subjects with ionized calcium ≤1.24 mmol/L showed higher RBC Aggregation. There was a positive correlation between HOMA-IR and RBC Aggregation and HOMA-IR showed a negative correlation with RBC deformability 0.30 Pa. Subjects with HOMA-IR <1.80 showed lower RBC aggregation and higher RBC deformability at 0.30 Pa, 0.60 Pa, 1.20 Pa, 3.0 Pa and 6.0 Pa. Conclusion: Low 25(OH)D, low ionized calcium and high HOMA-IR are related to impaired hemorheology in menopause. RBC aggregation and deformability can be used as biomarkers of calcium metabolism and insulin resistance in menopause. Show more

Keywords: Hemorheology, calcium metabolism, osteoporosis, vitamin D, insulin resistance, cardiovascular diseases

DOI: 10.3233/CH-200956

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2020

Authors: Boisson, Camille | Rab, Minke A.E. | Nader, Elie | Renoux, Céline | van Oirschot, Brigitte A. | Joly, Philippe | Fort, Romain | Stauffer, Emeric | van Beers, Eduard J. | Sheehan, Vivien A. | van Wijk, Richard | Connes, Philippe

Article Type: Research Article

Abstract: Sickle cell disease (SCD) is a genetic disorder characterized by the production of an abnormal hemoglobin (Hb), which, under deoxygenation, may polymerize and cause a mechanical distortion of red blood cell (RBC) into a crescent-like shape. Recently a method, using ektacytometry principle, has been developed to assess RBC deformability as a function of oxygen tension (pO2 ) and is called oxygen gradient ektacytometry (oxygenscan). However, standardization of this test is needed to properly assess the tendency of sickling of RBCs under deoxygenation and to allow comparisons between different laboratories. The study compared the oxygenscan responses during blood storage between distinct …populations of SCD patients. Blood from 40 non-transfused homozygous SCD patients (HbSS), 16 chronically transfused HbSS patients, and 14 individuals with compound heterozygous hemoglobin SC disease (HbSC)at steady-state was collected in EDTA tubes. Measurements were performed within 4 hours after collection and after 24 hours of storage at 4°C. We showed that storage affected the minimum RBC deformability reached during deoxygenation (EImin) in both non-transfused HbSS and HbSC patients and the maximum RBC deformability (EImax) measured before deoxygenation (i.e., in normoxia) in the three groups. In contrast, the tendency of RBCs to sickle under deoxygenation (i.e., the point of sickling; PoS) remained rather stable between the two time of measurements. Collectively, since the time between blood sampling and analysis affects some key oxygen gradient ektacytometry-derived parameters we recommend that each laboratory performs oxygenscan measurements at a standardized time point. Show more

Keywords: Oxygen gradient ektacytometry, sickle cell disease, red blood deformability, storage

DOI: 10.3233/CH-201037

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-4, 2020

Authors: Xiao, Huang | Pengfei, Chen | Fakuan, Tang | Ning, Hua

Article Type: Research Article

Abstract: BACKGROUD: Patients with chest pain and suspected of coronary artery disease(CAD) need further test to confirm the diagnosis. Magnetocardiography (MCG) is a non-invasive and emission-free technology which can detect and measure the weak magnetic fields created by the electrical activity of the heart. OBJECTIVE: This study aimed to investigate the usefulness of the 10 MCG parameters to detect CAD in patients with chest pain by means of a machine learning method of multilayer perceptron(MLP) neural network. METHODS: 209 patients who were suffering from chest pain and suspected of CAD were enrolled in this cross-sectional study. In …all patients, 12-lead electrocardiography(ECG) and MCG test were performed before percutaneous coronary angiography(PCA). 10 MCG parameters were analyzed by MLP neural networks. RESULTS: 11 diagnostic models(M1 to M11) were established after MLP analysis. The accuracies ranged from 71.2% to 90.5%. Two models(M10 and M11) were further analyzed. The accuracy, sensitivity, specificity, PPV, NPV, PLR and NLR were 89.5%, 89.8%, 88.9%, 92.7%, 84.7%, 11.10 and 0.11, of M10, and were 90.0%, 91.4%, 87.7%, 92.1%, 86.6%, 7.43 and 0.10, of M11. CONCLUSIONS: By a method of MLP neural network, MCG is applicable in identifying CAD in patients with chest pain, which seems beneficial for detection of CAD. Show more

Keywords: Magnetocardiography, percutaneous coronary intervention, coronary artery disease, diagnosis, machine learning

DOI: 10.3233/CH-200905

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2020

Authors: Braune, S. | Bäckemo, J. | Lau, S. | Heuchel, M. | Kratz, K. | Jung, F. | Reinthaler, M. | Lendlein, A.

Article Type: Research Article

Abstract: Nanoporous microparticles prepared from poly(ether imide) (PEI) are discussed as candidate adsorber materials for the removal of uremic toxins during apheresis. Polymers exhibiting such porosity can induce the formation of micro-gas/air pockets when exposed to fluids. Such air presenting material surfaces are reported to induce platelet activation and thrombus formation. Physical or chemical treatments prior to implantation are discussed to reduce the formation of such gas nuclei. Here, we report about the influence of different rewetting procedures – as chemical treatments with solvents – on the thrombogenicity of hydrophobic PEI microparticles and PEI microparticles hydrophilized by covalent attachment of poly(vinyl …pyrrolidone) (PVP) of two different chain lengths. Autoclaved dry PEI particles of all types with a diameter range of 200 – 250 μm and a porosity of about 84% ±2% were either rewetted directly with phosphate buffered saline (24 h) or after immersion in an ethanol-series. Thrombogenicity of the particles was studied in vitro using human sodium citrated whole blood (60 min, 5 rpm vertical rotation). Numbers of non-adherent platelets were quantified, and adhesion of blood cells was qualitatively analyzed by bright field microscopy. Platelet activation (percentage of CD62P positive platelets and amounts of soluble P-Selectin) and platelet function (PFA100 closure times) were analysed. Retention of blood platelets on the particles was similar for all particle types and both rewetting procedures. Non-adherent platelets were less activated after contact with ethanol-treated particles of all types compared to those rewetted with phosphate buffered saline as assessed by a reduced number of CD62P-positive platelets and reduced amounts of secreted P-Selectin (P  < 0.05 each). Interestingly, the hydrophilic surfaces significantly increased the number of activated platelets compared to hydrophobic PEI regardless of the rewetting agent. This suggests that, apart from wettability, other material properties might be more important to regulate platelet activation. PFA100 closure times were reduced and within the reference ranges in the ethanol group, however, significantly increased in the saline group. No substantial difference was detected between the tested surface modifications. In summary, rewetting with ethanol resulted in a reduced thrombogenicity of all studied microparticles regardless of their wettability, most likely resulting from the evacuation of air from the nanoporous particles. Show more

Keywords: Biomaterial, polymer, microparticle, thrombogenicity, hemocompatibility, dynamic in-vitro test, rewetting

DOI: 10.3233/CH-201029

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2020

Authors: Liu, Qin | Wang, Zhengrong

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the diagnostic value of real-time shear wave elastography (SWE) in children with chronic kidney disease (CKD). METHODS: Children with CKD diagnosed by the ultrasound-guided biopsy between January 2018 and May 2019 were enrolled as the case group. Age- and sex- matched healthy children were selected as the control group. The Young’s Modulus (YM) of the renal cortex was measured by SWE after the traditional ultrasound examination. Variance analysis was performed to compare the values of YM between the two groups. Receiver operating characteristic curve (ROC) analysis was used to compare the values of YM, and …explore the cut-offs of the YM. RESULTS: In the case group (n  = 60, 45% male, mean age of 9.2 years), the kidney YM modulus on the left side (16.8±4.8 kPa vs. 8.3±2.1 kPa) and the right side (16.0±4.7 kPa vs. 8.3±2.4 kPa) were both higher than the control group (all P values <  0.001). With the progress of CKD, the YM value of the left and right kidneys gradually increased. ROC analysis showed that when the left and right kidney YM value was 11.7 kPa and 11.0 kPa, the diagnostic sensitivity and specificity were the highest (left: respectively 93.3% and 95.0%; right: respectively 93.3 % and 91.7%). CONCLUSION: The increase of YM in CKD is related to the progression of renal dysfunction which may provide a new method for early diagnosis of CKD, dynamic monitoring of disease progression, and evaluation of curative effect and prognosis. Show more

Keywords: Shear wave elastography, chronic kidney disease, children

DOI: 10.3233/CH-200982

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2020

Authors: Krüger-Genge, A. | Tondera, C. | Hauser, S. | Braune, S. | Görs, J. | Roch, T. | Klopfleisch, R. | Neffe, A.T. | Lendlein, A. | Pietzsch, J. | Jung, F.

Article Type: Research Article

Abstract: Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the “Hen’s egg test on chorioallantoic membrane” (HET-CAM) test and a mouse model. The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well …as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants. Show more

Keywords: Gelatin-based hydrogels, immune cells, platelets, in vitro testing, mouse model

DOI: 10.3233/CH-201028

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2020

Authors: Chen, Ji-Xiong | Huang, Xiao-Yan | Wang, Ping | Lin, Wen-Ting | Xu, Wen-Xing | Zeng, Min

Article Type: Research Article

Abstract: This study aimed to investigate the effects of arachidonic acid metabolite epoxyeicosatrienoic acid (EETs) in the apoptosis of endothelial cells induced by tumor necrosis factor-alpha (TNF-α ). After human umbilical vein endothelial cells were cultured, TNF-α /ActD, 14, 15-EET, and HMR-1098 were added, respectively, into the culture medium. The apoptosis level of endothelial cells was detected by flow cytometry. After TNF-α /ActD induced endothelial cell apoptosis, flow cytometry staining showed that endothelial cell apoptosis increased significantly, and the apoptotic cells were significantly reduced after the addition of 14, 15-EET. However, the apoptotic cells significantly increased after the addition of HMR-1098. …Western Blot results showed that the phosphorylation levels of LC3-II and AMPK were increased after TNF-α /ActD induction, and the increase was noticeable after the addition of 14, 15-EET. However, the phosphorylation levels of LC3-II and AMPK significantly decreased after the addition of HMR-1098. The activity of Caspase-8 and -9 decreased significantly after the addition of 14, 15-EET but increased after the addition of HMR-1098. Arachidonic acid can inhibit TNF-α induced endothelial cell apoptosis by upregulating autophagy. Show more

Keywords: Epoxyeicosatrienoic acid, autophagy, apoptosis, endothelial cell, TNF-α

DOI: 10.3233/CH-200946

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2020

Authors: Zhao, Dan | Shao, Ya-Qin | Hu, Jun | Liu, Dan | Tang, Wei | He, Ning

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the diagnostic value of core-needle biopsy (CNB) guided by contrast-enhanced ultrasound (CEUS) in cervical tuberculous lymphadenitis (CTL). METHODS: 178 patients with pathological confirmation of CTL were retrospectively enrolled. All of them had undergone CNB prior to the final surgery. According to the different ways of puncture guidance, they were divided into two groups: conventional ultrasound (US) group (n  = 81) and CEUS group (n  = 97). The comparison of diagnostic efficacy between two groups was compared and analyzed. RESULTS: Among the 178 patients, 146 were directly diagnosed as CTL by CNB, including 59 patients in …CEUS group and 87 patients in US group. The diagnostic accuracy were 89.7% (87/97) and 72.8% (59/81), respectively (P  <  0.01). For subgroup analyses, differences among diagnostic efficacy ascribed to the different guiding methods were significant in medium size group (>2.0 cm and ≤3.0 cm) and large size group (>3.0 cm), 91.7% for CEUS group vs. 69.0% for US group (P  <  0.05) and 84.4% for CEUS group vs. 57.7% for US group (P  <  0.05), respectively. CONCLUSIONS: In the diagnosis of CTL, compared with the US-guided CNB, CEUS-guided CNB have certain advantages, especially for larger lymph nodes. Show more

Keywords: Contrast-enhanced ultrasound, ultrasound, core-needle biopsy, tuberculous lymphadenitis, cervical

DOI: 10.3233/CH-201038

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2020

Authors: Jung, Ernst Michael | Engel, Martin | Wiggermann, Philipp | Schicho, Andreas | Lerchbaumer, Markus | Stroszczynski, Christian | Fischer, Thomas | Wiesinger, Isabel

Article Type: Research Article

Abstract: AIM: The aim of this study was to assess the success of irreversible electroporation (IRE) in prostate cancer and to differentiate between reactive changes and tumor. MATERIAL AND METHODS: This is a retrospective pilot study of 50 patients after irreversible electroporation (IRE) in prostate cancer between 50–79 years (mean age 65 years). Each patient received a transabdominal sonography using a 1–6 MHz convex matrix probe. Contrast-enhanced ultrasound (CEUS) was performed after i.v. bolus injection of 2.0 ml sulphur hexafluoride microbubbles. DICOM loops were continuously stored up to one minute. Parametric images were calculated by integrated perfusion analysis software. A …comparison was drawn to a follow-up MRI six months after ablation. RESULTS: While 13 patients showed local recurrence, 37 patients were successfully treated, meaning no local recurrence within six months after ablation. 18 patients showed signs of prostatitis after IRE. Tumorous changes were visually characterized by dynamic early nodular hypervascularization with fast and high wash-in. Correspondingly, nodular red and yellow shades were seen in parametric imaging. All patients with remaining tumor were correctly identified with CEUS and parametric imaging. After IRE there is a relevant decrease in tumor microcirculation in all patients, as seen in more purple shades of the prostate. The sensitivity for detecting residual tumor with CEUS compared to MRI was 76 %, the specificity was 81 %. The corresponding positive predictive value (PPV) was 73 % and the negative predictive value (NPV) was 83 %. CONCLUSION: CEUS and parametric imaging enable a critical analysis of post-ablation defects after IRE for prostate cancer even with a transabdominal approach. Remaining tumor can be detected with the help of pseudo-colors. Show more

Keywords: Parametric imaging, CEUS, prostate cancer, IRE

DOI: 10.3233/CH-201000

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2020

Authors: Peschel, G. | Jung, E.M. | Fisser, C. | Putz, F.J. | Wertheimer, T. | Sinner, B. | Lunz, D. | Jung, F. | Müller, M.

Article Type: Research Article

Abstract: BACKGROUND: Coronavirus disease 2019 (COVID-19) can cause acute respiratory distress Syndrome (ARDS). OBJECTIVE: This single centre cross-section study aimed to grade the severity of pneumonia by bed-side lung ultrasound (LUS). METHODS: A scoring system discriminates 5 levels of lung opacities: A-lines (0 points),≥3 B-Line (1 point), coalescent B-Lines (2 points), marked pleural disruptions (3 points), consolidations (4 points). LUS (convex 1–5 MHz probe) was performed at 6 defined regions for each hemithorax either in supine or prone position. A lung aeration score (LAS, maximum 4 points) was allocated for each patient by calculating the arithmetic mean of …the examined lung areas. Score levels were correlated with ventilation parameters and laboratory markers. RESULTS: LAS of 20 patients with ARDS reached from 2.58 to 3.83 and was highest in the lateral right lobe (Mean 3.67). Ferritin levels (Mean 1885μg/l; r  = 0.467; p  = 0.051) showed moderate correlation in spearman roh calculation. PaCO2 level (Mean 46.75 mmHg; r  = 0.632; p  = 0.005) correlated significantly with LAS, while duration of ventilation, Horovitz-Index, CRP, LDH and IL-6 did not. CONCUSIONS: The proposed LAS describes severity of lung opacities in COVID-19 patients and correlates with CO2 retention in patients with ARDS. Show more

Keywords: COVID-19, lung ultrasound, scoring system, PaCO2

DOI: 10.3233/CH-200925

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020