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

Authors: Li, Bao-Hua | Fang, Kuai-Fa | Lin, Pei-Huan | Zhang, Yi-Hui | Huang, Yong-Xiang | Jie, Hai

Article Type: Research Article

Abstract: OBJECTIVE: The aim of the present study was to observe the effect of sacubitril valsartan on cardiac function and vascular endothelial function in patients with chronic heart failure with reduced ejection fraction (HFrEF). METHODS: A total of 80 patients with HFrEF were randomly divided into an observation group and a control group, with 40 patients in each group. Sacubitril valsartan was added to the conventional treatment in the observation group, and perindopril was added to the conventional treatment in the control group. Both groups were treated continuously for 12 weeks. The left ventricular ejection fraction (LVEF), left ventricular …end-diastolic diameter (LVEDD), flow-mediated vasodilatory function (FMD) of the brachial artery, and levels of plasma Ang II, endothelin 1 (ET-1), and calcitonin gene-related peptide (CGRP), together with the serum nitric oxide (NO) and NO synthase (NOS) were compared before and after treatment in the groups. RESULTS: Before the treatment, the levels of LVEF, LVEDD, FMD, Ang II, ET-1, CGRP, NO, and NOS in the observation group were not significantly different from those in the control group (P  >  0.05). However, the levels of LVEF, FMD, CGRP, NO, and NOS in both groups were significantly higher after the treatment than those before the treatment (P  <  0.05) and significantly higher in the observation group than those in the control group. The difference was statistically significant (P  <  0.05). Meanwhile, the levels of LVEDD, Ang II, and ET-1 in both groups decreased significantly after the treatment (P  <  0.05) and were significantly lower in the observation group than those in the control group. The difference was statistically significant (P  <  0.05). CONCLUSION: Sacubitril valsartan might improve endothelial function while increasing cardiac function in HFrEF patients. Show more

Keywords: Sacubitril valsartan, left ventricular ejection fraction, chronic heart failure, cardiac function, endothelial function

DOI: 10.3233/CH-201032

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

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

Authors: Bachour, Yara

Article Type: Letter

DOI: 10.3233/CH-201012

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 2020

Authors: Hoesl, V.

Article Type: Letter

DOI: 10.3233/CH-201023

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 2020

Authors: Dan, Zuo | Yi, Feng | Qi, Zhang | Yi-Jie, Qiu | Xiao-Fan, Tian | Shuai-Nan, Shi | Yi, Dong | Tian-Shu, Liu | Wen-Ping, Wang

Article Type: Research Article

Abstract: PURPOSE: To evaluate the feasibility of dynamic contrast enhanced ultrasound (DCE-US) in predicting treatment response of high-intensity focused ultrasound (HIFU) in patients with locally advanced pancreatic cancer (LAPC) lesions. PATIENTS AND METHODS: In this prospective study, 10 patients with pathologically confirmed LAPC lesions (7 men, 3 women; average age, 61.13±5.80 years) were prospectively enrolled. All patients received HIFU treatment with peak intensity at 12000 W/cm2 . Contrast enhanced ultrasound (CEUS) was performed with an ACUSON Oxana 2 ultrasound equipment and a 6 C-1 transducer (1–6 Hz). A dose of 2.4 ml SonoVue was injected for each examination. Time intensity curves (TICs) …were generated and quantitative analyses were performed by SonoLiver software. B mode ultrasound (BMUS) features, CEUS enhancement patterns, TICs, CEUS quantitative parameters and serum carcinoma antigen 19-9 (CA19-9) levels were compared before and 4 weeks after HIFU treatment. Statistical analyses were performed with SPSS Version 20.0 and GraphPad Prism 5. RESULTS: While comparing before and after HIFU, no significant difference was obtained on mean size of lesion, BMUS or CEUS features. After HIFU treatment, TICs showed decreased and delayed enhancement. Among all CEUS quantitative parameters, significant decrease could be found in maximum intensity (MI) (60.66±23.95% vs 41.31±26.74%) and mean transit time (mTT) (76.66±47.61 s vs 38.42±28.35 s). CA19-9 level decreased significantly after HIFU (2747.92±4237.41 U/ml vs 715.08±1773.90 U/ml) (P  = 0.05). CONCLUSION: DCE-US combining with quantitative analysis might be a useful imaging method for early treatment response evaluation of HIFU in LAPC lesions. Show more

Keywords: Dynamic contrast enhanced ultrasound (DCE-US), locally advanced pancreatic cancer (LAPC), high-intensity focused ultrasound (HIFU), therapeutic response, blood perfusion

DOI: 10.3233/CH-201020

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

Authors: Luo, Zhi-Yan | Hong, Yu-Rong | Yan, Cao-Xin | Wang, Yong | Ye, Qin | Huang, Pintong

Article Type: Research Article

Abstract: OBJECTIVES: The aim of this study was to find the optimal parameters and cutoffs to differentiate metastatic lymph nodes (LNs) from benign LNs in the patients with papillary thyroid carcinoma (PTC) on the quantitative contrast-enhanced ultrasound (CEUS) features. METHODS: A total of 134 LNs in 105 patients with PTCs were retrospectively enrolled. All LNs were evaluated by conventional ultrasound (US) and CEUS before biopsy or surgery. The diagnostic efficacy of CEUS parameters was analyzed. RESULTS: Univariate analysis indicated that metastatic LNs more often manifested centripetal or asynchronous perfusion, hyper-enhancement, heterogeneous enhancement, ring-enhancing margins, higher PI, …larger AUC, longer TTP and DT/2 than benign LNs at pre-operative CEUS (p  <  0.001, for all). Multivariate analysis showed that centripetal or asynchronous perfusion (OR = 3.163; 95% CI, 1.721–5.812), hyper-enhancement(OR = 0.371; 95% CI, 0.150–0.917), DT/2 (OR = 7.408; 95% confidence interval CI, 1.496–36.673), and AUC (OR = 8.340; 95% CI, 2.677–25.984) were predictive for the presence of metastatic LNs. The sensitivity and accuracy of the quantitative CEUS were higher than qualitative CEUS (75% vs 55 % and 83.6% vs 76.1 % , respectively). CONCLUSIONS: Quantitative CEUS parameters can provide more information to distinguish metastatic from benign LNs in PTC patients; In particular, DT/2 and AUC have a higher sensitivity and accuracy in predicting the presence of metastatic LNs and reduce unnecessary sampling of benign LNs. Show more

Keywords: Contrast-enhanced ultrasound, lymph node metastasis, papillary thyroid carcinoma, ultrasound

DOI: 10.3233/CH-200909

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Lu, Dian Yuan | Liu, Lan | Shen, Li | Cai, Jian Rong | Xu, Li | Xiang, Li Hua

Article Type: Research Article

Abstract: OBJECTIVE: To investigate prostate cancer detection rate of different biopsy protocols in different PSA value groups in rural China. METHODS: A total of 186 patients underwent contrast-enhanced ultrasound (CEUS) in order to determine the puncture target prior to biopsy were enrolled in this retrospective study. All patients underwent 12-core SB combined with CEUS-TB. The biopsy results of different biopsy protocols were compared in patients with stratification by PSA value. RESULTS: Among the 186 patients underwent prostate biopsy, the histopathologic results revealed prostate cancer (PCa) in 117 cases (62.9%) and benign lesions in 69 cases (37.1%). The …PCa detection rate between 8-core SB and 12-core SB showed no significant difference in PSA 4–10 ng/ml group, while the 12-core SB was significantly higher than CEUS-TB (44.9% versus 32.7% , P  = 0.01). In PSA 10–20 ng/ml group, the significant difference was not seen between SB and CEUS-TB (50.0% versus 45.7% , P  = 0.15). As for PSA greater than 20 ng/ml group, the PCa detection rate by SB was higher than CEUS-TB, but showed no statistically significance (79.1% versus 76.9% , P  = 0.15). In the overall patients, the biopsy core positive rate of CEUS-TB was significantly higher than SB (97% versus 55.5% and 28.5% , P  = 0.0001). CONCLUSION: The flexible use of SB combined with CEUS-TB can reduce the number of biopsy cores in higher PSA groups. It has clinical importance in the detection of PCa in different PSA value groups in rural China. Show more

Keywords: PSA value, contrast-enhanced ultrasound, systematic biopsy, CEUS-targeted biopsy, prostate cancer

DOI: 10.3233/CH-200993

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

Authors: Joly, Philippe | Bonello-Palot, Nathalie | Badens, Catherine | Pissard, Serge | Chamouine, Abdourahim | Bernaudin, Françoise | Bertrand, Yves | Connes, Philippe | Renoux, Céline

Article Type: Research Article

Abstract: Sickle cell anemia (SCA) is a disease characterized by abnormal red blood cell rheology. Because of their effects on HbS polymerization and red blood cell deformability, alpha-thalassemia and the residual HbF level are known genetic modifiers of the disease. The aim of our study was to determine if the number of HbF quantitative trait loci (QTL) would also favor a specific sub-phenotype of SCA as it is the case for alpha-thalassemia. Our results confirmed that alpha-thalassemia protected from cerebral vasculopathy but increased the risk for frequent painful vaso-occlusive crises. We also showed that more HbF-QTL may provide an additional and …specific protection against cerebral vasculopathy but only for children with alpha-thalassemia (-α /α α or -α /-α genotypes). Show more

Keywords: SCA, HbF quantitative trait loci, XmnI, BCL11A, HBS1L-MYB, cerebral vasculopathy, alpha-globin genotype

DOI: 10.3233/CH-200951

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2020

Authors: Lian, Kai-Mei | Lin, Teng

Article Type: Research Article

Abstract: Purpose: The value of virtual touch tissue imaging (VTI) with support of Image-Pro Plus (IPP) for diagnosing malignant thyroid tumors was assessed in the present study. Methods: In this retrospective study, we enrolled 160 patients with 198 thyroid nodules. TI-RADS, VTI grade, and VTI with support of IPP (VTI-IPP) were underwent for each nodule. With the pathological diagnosis as the gold standard, the receiver-operating characteristic curve (ROC) was drawn to evaluate the diagnostic performance of VTI-IPP, VTI, TI-RADS, VTI-IPP combinate with TI-RADS in thyroid carcinoma. Results: VTI-IPP score >2, VTI score >3, TI-RADS score >1, and …VTI-IPP combine with TI-RADS score >4 expressed the highest diagnostic value for malignant thyroid nodules, the areas under the curve (AUC) were 0.939, 0.905, 0.925, and 0.967, respectively. The combination indicated the largest AUC, compared with VTI-IPP and TI-RADS, respectively (P  = 0.0054 and 0.0009). The performance of VTI-IPP in diagnosing thyroid carcinomas was better than VTI (P  = 0.0321). Conclusion: Compare with VTI, VTI-IPP exhibited more excellent value in distinguishing between benign and malignant thyroid nodules. The value of malignant thyroid nodules diagnosis can be improved when VTI-IPP combines with TI-RADS. Show more

Keywords: Thyroid nodules, virtual touch tissue image, thyroid imaging reporting and data system, Image-Pro Plus

DOI: 10.3233/CH-200983

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

Authors: Zhou, Ya-Fang | Zhang, Yi-Feng | Fu, Hui-Jun | Yang, Wei-Ping | Zhao, Chong-Ke | Xu, Hui-Xiong

Article Type: Research Article

Abstract: Purpose: To propose a diagnostic algorithm for improving the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) thyroid nodules. Methods: This study retrospectively enrolled 77 consecutive patients with 81 AUS/FLUS nodules who underwent preoperative BRAFV600E mutation analysis. A new diagnostic algorithm was proposed that BRAFV600E mutation analysis for the Fine-needle aspiration cytology specimen was firstly carried out, in which positive BRAFV600E mutation indicated malignancy and classification of the nodules with negative BRAFV600E mutation was further performed based on ultrasound pattern-based risk stratification of American Thyroid Association Guidelines. The diagnostic …performance of the new diagnostic algorithm was evaluated. Results: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under the receiver operating characteristic curve (AUROC) of new diagnostic algorithm were 94.6%, 84.0%, 91.4%, 86.9%, 90.1%, and 0.893, respectively. The proposed diagnostic algorithm significantly increased the diagnostic performances (AUROC: 0.893 vs. 0.837 and 0.795), sensitivity (94.6% vs. 71.4% and 75.0%), and accuracy (90.1% vs. 79.0% and 77.8%) compared with BRAFV600E mutation analysis alone and ultrasound pattern-based risk stratification alone (all P  <  0.05). Conclusion: The proposed diagnostic algorithm is helpful for improving the diagnosis of AUS/FLUS nodules, which might be as a routine approach. Show more

Keywords: Thyroid nodules, fine-needle aspiration cytology, AUS/FLUS nodule, BRAF, V600E analysis, ultrasound pattern-based risk stratification

DOI: 10.3233/CH-200985

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2020

Authors: Brunacci, Nadia | Wischke, Christian | Naolou, Toufik | Patzelt, Alexa | Lademann, Jürgen | Neffe, Axel T. | Lendlein, Andreas

Article Type: Research Article

Abstract: The size of particulate carriers is key to their transport and distribution in biological systems, and needs to be tailored in the higher submicron range to enable follicular uptake for dermal treatment. Oligodepsipeptides are promising nanoparticlulate carrier systems as they can be designed to exhibit enhanced interaction with drug molecules. Here, a fabrication scheme for drug-loaded submicron particles from oligo[3-(S)-sec -butylmorpholine-2,5-dione]diol (OBMD) is presented based on an emulsion solvent evaporation method with cosolvent, surfactant, and polymer concentration as variable process parameters. The particle size (300–950 nm) increased with lower surfactant concentration and higher oligomer concentration. The addition of acetone increased the …particle size at low surfactant concentration. Particle size remained stable upon the encapsulation of models compounds dexamethasone (DXM) and Nile Red (NR), having different physicochemical properties, DXM was released faster compared to NR due to its higher water solubility. Overall, the results indicated that both drug-loading and size control of OBMD submicron particles can be achieved. When applied on porcine ear skin samples, the NR-loaded particles have been shown to allow NR penetration into the hair follicle and the depth reached with the 300 nm particles was comparable to the one reached with the cream formulation. A potential benefit of the particles compared to a cream is their sustained release profile. Show more

Keywords: Submicron particles, oligodepsipeptide, formulation parameters, emulsion solvent evaporation, surfactant, release kinetics

DOI: 10.3233/CH-200977

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-19, 2020

Authors: Alzoughool, Foad | Alanagreh, Lo’ai | Abumweis, Suhad | Atoum, Manar

Article Type: Research Article

Abstract: The emerging coronavirus disease (COVID-19) swept the world, affecting more than 200 countries and territories. As of August 22, 2020, the pandemic infected more than 23,329,752 including 807,054 patients who have died. Although the main clinical features of the pandemic disease are respiratory, cerebrovascular comorbidities emerged as one of the leading causes of death associated with COVID-19. Different case reports have indicated that C-reactive protein (CRP) and D-dimer (pro-inflammatory biomarkers) were elevated in COVID-19 patients, which can significantly increase the risk of ischemic stroke. Available data on cerebrovascular complications in COVID-19 patients were collected and a meta-analysis was designed and …carried out to evaluate the risk of severity and mortality associated with high levels of CRP and D-dimer levels in COVID-19 patients. In addition, we aimed to describe the overall event rate of pre-existing cerebrovascular disease in COVID-19 patients. In our analysis, 5,614 cases have been studied, out of these patients 164 cases have developed cerebrovascular comorbities. Cerebrovascular comorbidity increased the risk of disease severity (odd ratio = 4.4; 95% CI: 1.48 to 12.84) and mortality (odd ratio = 7.0; 95% CI: 2.56 to 18.99). Statistical analyses showed that CRP and D-dimer serum levels were elevated by six-folds in the severe cases of COVID-19 patients. This significant increase in these two proteins levels can serve as a vital indicator for COVID-19 patients who are at increased risk of severe COVID-19 cerebrovascular complications, such as stroke. Show more

Keywords: Cerebrovascular disease, COVID-19, Stroke, C - reactive protein, D-dimer

DOI: 10.3233/CH-201002

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Zhao, Meng | Zhu, Yunkai | Zhang, Yanhua | Yang, Xupeng | Duan, Yourong | Chen, Yaqing | Sun, Ying

Article Type: Research Article

Abstract: BACKGROUND: Molecular targeted contrast-enhanced ultrasound (CEUS) imaging is a potential imaging strategy to improve the diagnostic accuracy of conventional ultrasound (US) imaging. US contrast agents are usually micrometer-sized and non-target gas bubbles while nano-sized and targeted agents containing phase-shift materials absorb more attractions for their size and the liquid core and excellent molecular imaging effect. METHODS: PLGA12k -mPEG2k -NH2 , DSPE-mPEG2k and perfluorohexan (PFH) were used to construct a new targeted ultrasound contrast agent with CUB domain-containing protein 1 (CDCP1) receptor for the detection and diagnosis of prostate cancer. The potential of tumor-targeted nanoparticles (CDCP1-targeted perfluorohexan-loaded phase-transitional …nanoparticles, anti-CDCP1 NPs) as contrast agents for ultrasound (US) imaging was assessed in vitro . Moreover, studies on the cytotoxicity and the targeting ability of anti-CDCP1 NPs assisted by US were carried out. RESULTS: The results showed that anti-CDCP1 NPs had low cytotoxicity, and with the increasing of polymer concentration in anti-CDCP1 NPs, the CEUS imaging of agent gradually enhanced, and enhanced imaging associated with the length of observing time. Furthermore, it was testified that anti-CDCP1 assisted the agent to target cells expressing CDCP1, which demonstrated the active targeting of anti-CDCP1 NPs in vitro . CONCLUSION: All in all, the feasibility of using targeted anti-CDCP1 NPs to enhance ultrasound imaging has been demonstrated in vitro , which laid a solid foundation for molecular US imaging in vivo , and anti-CDCP1 NPs might have a great clinical application prospect. Show more

Keywords: Targeted nanoparticle, contrast agent, prostate cancer

DOI: 10.3233/CH-200900

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

Authors: Yurtdaş, Mustafa | Asoğlu, Ramazan | Özaydın, Adnan

Article Type: Research Article

Abstract: BACKGROUND: Inflammation has an important role in the pathogenesis of atherosclerosis. Lymphocyte-to-monocyte ratio (LMR) is accepted as an indicator of inflammation. OBJECTIVE: Our aim was to scrutinize the relationship between LMR and subclinical atherosclerosis (SubAth) measured by carotid intima-media thickness (CIMT) in subclinical hypothyroidism (SubHT). METHODS: Newly identified 190 SubHT patients were prospectively included into the study. Blood samples were taken for measuring laboratory parameters. Then, CIMT was computed. Patients were seperated into 2 groups by their CIMT value (Group-1: ≤0.9 and Group-2: >0.9 mm), and then stratified into tertiles pursuant to LMR and thyroid-stimulating hormone (TSH) …levels, respectively. RESULTS: 59 patients had an increased CIMT value (Group-2), and 131 patients had a normal CIMT value (Group-1). Group-2 had a lower LMR and a greater high-sensitivity C-reactive protein (hsCRP), CIMT and TSH than Group-1 (for all, p  <  0.05). Patients in the lowest tertile of LMR had a higher hsCRP, TSH and CIMT than those in the highest tertile (for all, p  <  0.05). LMR was negatively associated with hsCRP, CIMT and TSH (for all, p  <  0.05). LMR and TSH were independent predictors of increased CIMT. CONCLUSIONS: Pre-ultrasonographic LMR, which is a simple and inexpensive inflammatory marker, may give additional predictive information to determine SubAth in SubHT. Show more

Keywords: Lymphocyte-to-monocyte ratio, carotid intima-media thickness, subclinical atherosclerosis, inflammation, subclinical hypothyroidism

DOI: 10.3233/CH-200820

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

Authors: Song, Kyojun | Yi, Ho Jun | Lee, Dong Hoon | Sung, Jae Hoon

Article Type: Research Article

Abstract: BACKGROUND: Elevated blood viscosity has been reported as a risk factor for cerebrovascular disease. OBJECTIVE: The relationship between blood viscosity and outcomes of mechanical thrombectomy (MT) for large artery occlusion (LAO) were investigated in the present study. METHODS: A total of 238 patients were enrolled and systolic blood viscosity (SBV) and diastolic blood viscosity (DBV) were measured using the scanning capillary tube viscometer. Receiver operating characteristic (ROC) analysis was performed to specify the association of viscosity with the first-pass reperfusion (FPR). Multivariable and regression analyses were performed to evaluate the relationship of viscosity with FPR and …various variables. RESULTS: Based on ROC analysis, the best DBV cutoff value was 10.55 (cP). In multivariable analysis, high DBV was associated with FPR failure (odds ratio 2.82, 95% confidence interval 1.64–4.22; p  = 0.001). Increased DVB could be associated with elevated SBV, hematocrit level, and blood urea nitrogen/creatinine ratio (p  = <0.001, 0.004, and 0.002, respectively). CONCLUSIONS: Elevated DBV was associated with FPR failure. Patients with high DBV had longer thrombus length and required more stent passages than patients with low DBV. Show more

Keywords: Blood viscosity, dehydration, ischemic stroke, reperfusion, risk factors, thrombectomy

DOI: 10.3233/CH-200979

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Zhang, Hui-Li | Meng, Hong-Bo | Li, Xiao-Long | Sun, Li-Ping | Lu, Feng | Xu, Hui-Xiong | Yu, Song-Yuan

Article Type: Research Article

Abstract: We described a patient with symptomatic giant hepatic hemangioma (GHH) treated with laparoscopic guided percutaneous microwave ablation (MWA). A 58 years’ old woman was referred to our hospital who presented with upper abdominal distension and appetite loss for more than 1 year. The medical history included untreated multiple hepatic hemangiomas (HH) that had been detected 13 years ago and hypertension for more than 12 years. Initial laboratory tests revealed D-dimer mild increase and negative tumor markers. Magnetic resonance (MR) imaging demonstrated multiple nodules of different sizes in the liver and the largest lesion was located on the left lobe (longest …diameter 12.8 cm), which replaced the whole enlarged left lobe and compressed the gastric body and inferior vena cava. Contrast-enhanced ultrasound (CEUS) and contrast-enhanced MR imaging both showed the typical enhancement pattern of hemangioma and abnormal perfusion was seen in the surrounding liver parenchyma. With the laparoscopy guidance, we performed microwave ablation till the whole tumor was seen atrophy. The total operation duration was 2 hours, with intra-operative blood loss less than 20 ml. The post-operative course was uneventful. The patient was discharged 3 days after the operation. Abdominal distension decreased, appetite improved, blood pressure controlled at normal level after the operation. MR revealed significant volume reduction of the tumor after the operation. Show more

DOI: 10.3233/CH-200922

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

Authors: Nugroho, Johanes | Wardhana, Ardyan | Mulia, Eka Prasetya | Maghfirah, Irma | Rachmi, Dita

Article Type: Research Article

Abstract: INTRODUCTION: COVID-19 is a systemic infection with a significant impact on coagulation which manifests in thromboembolism. There is an unknown relationship of which coagulation profile parameter at presentation has an association with poor outcome in COVID-19. OBJECTIVE: This meta-analysis aimed to determine the relationship between fibrinogen and FDP with poor outcome in COVID-19 patients. METHODS: A systematic search of all observational studies or trials involving adult patients with COVID-19 that had any data fibrinogen or FDP on admission was carried out using the PubMed, Science Direct, Scopus, ProQuest, and MedRxiv databases. We assessed the methodological quality …assessment using the NIH Quality Assessment Tool. We performed random-effects inverse-variance weighting analysis using mean difference (MD). RESULTS: A total of 17 studies (1,654 patients) were included in this meta-analysis. It revealed a higher mean of fibrinogen levels on admission in patients with severe case compared to those with non-severe case (MD = 0.69, [95% CI: 0.44 to 0.94], p  <  0.05; I2 = 72%, p  <  0.05). Non-survivor group had a pooled higher mean difference of fibrinogen values on admission (MD = 0.48 [95% CI: 0.13 to 0.83], p  <  0.05; I2 = 38%, p  = 0.18). Higher FDP on admission was found in poor outcome (composite of severity, critically ill, and mortality) compared to good outcome (4 studies, MD = 4.84 [95% CI: 0.75 to 8.93], p  <  0.05; I2 = 86%, p  <  0.05). CONCLUSION: Elevated fibrinogen and FDP level on admission were associated with an increase risk of poor outcome in COVID-19 patients. Show more

Keywords: COVID-19, fibrinogen, fibrin degradation product, severity, mortality, prognostic factor

DOI: 10.3233/CH-200978

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

Authors: Shen, Zijian | Li, Haigang

Article Type: Research Article

Abstract: BACKGROUND: Long non-coding RNAs (lncRNAs) are found to involve in modulating the development of atherosclerosis (AS). But the molecular mechanism of lncRNA growth-arrest specific transcript 5 (GAS5) in AS is not fully understood. METHODS: QRT-PCR was performed to measure the abundances of GAS5, miR-128-3p and fibulin 2 (FBLN2). Oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells were employed as cell models of AS. The cell proliferation and apoptosis were analyzed using CCK-8 and Flow cytometry assays, respectively. Levels of all protein were examined by western blot. The interaction among GAS5, miR-128-3p and FBLN2 was confirmed via dual-luciferase reporter and RNA …immunoprecipitation (RIP) assays. RESULTS: GAS5 was elevated and miR-128-3p was decreased in the serum of patients with AS and ox-LDL-stimulated THP-1 cells. Ox-LDL stimulation inhibited proliferation and induced apoptosis of THP-1 cells. Meanwhile, GAS5 directly targeted miR-128-3p and inversely modulated its expression. Importantly, GAS5 depletion facilitated cell proliferation and impaired apoptosis in ox-LDL-induced THP-1 cells. Additionally, GAS5 augmented FBLN2 expression through sponging miR-128-3p, and miR-128-3p facilitated proliferation and retarded apoptosis of ox-LDL-induced THP-1 cells by targeting FBLN2. CONCLUSION: GAS5 knockdown promoted the growth of ox-LDL-induced THP-1 cells through down-modulating FBLN2 and increasing miR-128-3p, suggesting the potential value of GAS5 for treatment of AS. Show more

Keywords: Atherosclerosis, ox-LDL, lncRNA GAS5, miR-128-3p, FBLN2

DOI: 10.3233/CH-200897

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Zhong, Li-Chang | Yang, Tian | Gu, Li-Ping | Ma, Fang

Article Type: Research Article

Abstract: PURPOSE: To evaluate the diagnostic value of shear wave velocity (SWV) ratio for the differential diagnosis of benign and malignant breast lesions. MATERIAL AND METHODS: Our retrospective study included 151 breast lesions that were diagnosed by biopsy and surgical pathology. All of the breast lesions were detected by conventional ultrasound and Virtual Touch tissue quantification (VTQ) and mammography. The sonographic characteristics of the breast lesion, such as the internal echo, shape, margin, color flow, and calcification so on, were also observed. The SWV in lesions and surrounding parenchyma were measured and the SWV ratio between the lesion and …surrounding parenchyma was calculated. Pathological results were used as a diagnosis standard to compare the value of SWV ratio, VTQ, and mammography in the diagnosis of benign and malignant breast lesions. RESULTS: The 151 breast lesions included 96 benign lesions and 55 malignant lesions. The cutoff value of VTQ in the diagnosis of benign and malignant breast lesions was 5.01 m/s, of SWV ratio was 2.43, and mammography was BI-RADS 4B. The sensitivity, specificity, accuracy and the area under the ROC curve (AUC) of the SWV ratio were 78.2%, 86.5%, 83.4%, and 0.83 respectively. While of SWV ratio with mammography was 86.4%, 89.4%, 88.3% and 0.87, respectively. The sensitivity, specificity, accuracy, and AUC of SWV ratio and SWV ratio with mammography were statistically higher than those of mammography, no statistically higher than VTQ and VTQ with mammography. CONCLUSION: The SWV ratio can improve the sensitivity without sacrificing diagnostic specificity in the process of breast cancer diagnostic, provide a better diagnostic performance, and avoid unnecessary biopsy or surgery. Show more

Keywords: Breast cancer, virtual touch tissue quantification, SWV ratio, mammography

DOI: 10.3233/CH-200813

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

Authors: Pillai, S. | Davies, G. | Lawrence, M.J. | Whitley, J. | Stephens, J.W. | Williams, P.R. | Morris, K. | Evans, P.A.

Article Type: Research Article

Abstract: BACKGROUND: Diabetic ketoacidosis (DKA) is a medical emergency with a high mortality rate and is associated with severe metabolic acidosis and dehydration. DKA patients have an increased risk of arterial and venous thromboembolism, however little is known about this metabolic derangement in the first 24 hours of admission and to assess its effect on coagulation. We therefore utilised a novel functional marker of clot microstructure (fractal dimension - d f ) to assess these changes within the first 24 hours. METHODS: Prospective single centre observational study to demonstrate whether the tendency of blood clot formation differs in …DKA patients. RESULTS: 15 DKA patients and 15 healthy matched controls were recruited. Mean d f in the healthy control group was 1.74±0.03. An elevated d f of 1.78±0.07 was observed in patients with DKA on admission. The mean pH on admission was 7.14±0.13 and the lactate was 3.6±2.0. d f changed significantly in response to standard treatment and was significantly reduced to 1.68±0.09 (2–6& h) and to 1.66±0.08 at 24& h (p  <  0.01 One-way ANOVA). d f also correlated significantly with lactate and pH (Pearson correlation coefficient 0.479 and –0.675 respectively, p  <  0.05). CONCLUSIONS: DKA patients at presentation have a densely organising less permeable thrombogenic clot microstructure as evidenced by high d f . These structural changes are due to a combination of dehydration and a profound metabolic acidosis, which was reversed with treatment. These changes were not mirrored in standard clinical markers of thromboge-nicity. Show more

Keywords: Diabetic ketoacidosis (DKA), haemorheology, fractal dimension, gel point

DOI: 10.3233/CH-200957

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Xu, Jialiang | Yu, Sijian | Zhang, Fuhua

Article Type: Research Article

Abstract: Thrombotic thrombocytopenic purpura (TTP) in adults is rare thrombotic microangiopathy (TMA), which is closely related to the lack of specific proteases of von Willebrand factor (vWF) multimers. It is currently believed that both congenital TTP (cTTP) and acquired TTP (aTTP) can induce acute attack through pregnancy. We report a case of a 24-year-old woman who was diagnosed as TTP during early pregnancy. A novel mutation was detected: c.3667G>T (p.E1223*). She responded well to plasma therapy during pregnancy and had a child by cesarean section at 32 weeks. TTP is still recurrent in postpartum patients. The plasma transfusion was effective, but …caused a severe transfusion reaction. Cyclosporine was administered with the consent of the patient. This case showed cyclosporine-A (CSA) had a positive effect on ADAMTS13 activity. At 11-months follow-up, the patient’s blood cells and LDH status were stable and no symptom was seen. Our case suggests that the patient had an unreported genetic mutation that causes TTP, immune factors may be involved in the onset of cTTP during pregnancy, and the use of immunosuppressive agents is effective in preventing recurrence. Show more

Keywords: Thrombotic thrombocytopenic purpura, ADAMTS13, pregnancy, genetic mutations, CSA

DOI: 10.3233/CH-200970

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2020

Authors: Shao, Sihui | Yao, Minghua | Li, Xin | Li, Chunxiao | Chen, Jing | Li, Gang | Jia, Chao | Wu, Rong

Article Type: Research Article

Abstract: OBJECTIVES: To evaluate the efficacy of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in differential diagnosis of sclerosing adenosis (SA) from malignance and investigate the correlated features with pathology. METHODS: We retrospectively enrolled 103 pathologically confirmed SA. All lesions were evaluated with conventional US while 31 lesions with CEUS. Lesions were divided into SA with or without benign lesions (Group 1, n  = 81) and SA with malignancy (Group 2, n  = 22). Performance of two methods were analyzed. The ultrasonographic characteristics were compared between two groups with Student’s t -test for measurement and chi-squared or Fisher’s exact test for …count data. RESULTS: There were 22 lesions complicated with malignancy, and the mean age of Group 2 was higher than Group 1 (55.27 vs. 41.57, p  <  0.001). The sensitivity, specificity and accuracy of conventional US and CEUS were 95.45%, 46.91%, 57.28% and 100%, 62.5%, 70.97%. Angularity (p  <  0.001), spicules (p  = 0.023), calcification (p  = 0.026) and enlarged scope (p  = 0.012) or crab claw-like enhancement (p  = 0.008) in CEUS were more frequent detected in SA with malignancy. CONCLUSIONS: Though CEUS showed an improved accuracy, the performance of ultrasound in the diagnosis of SA was limited. Awareness and careful review of the histopathologically related imaging features can be helpful in the diagnosis of SA. Show more

Keywords: Adenosis of breast, breast cancer, breast ultrasonography

DOI: 10.3233/CH-200943

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

Authors: Jung, Ernst | Hösl, Vanessa | von Fraunberg, Sarah | Jung, Friedrich | Prantl, Lukas

Article Type: Research Article

Abstract: BACKGROUND: Capsular contractures around breast implants usually develop leading to pain and aesthetically inadequate results and ultimately often requires the replacement of the implants. Textured silicone implants are the most commonly placed implant, but polyurethane-coated implants are increasingly being used in an attempt to ameliorate the long-term complications associated with implant insertion. AIM: Capsular contracture is traditionally classified using the Baker scale, a subjective classification system based upon clinical findings. Aim of this study was to evaluate the association between pain due capsular contraction, Baker Score and different techniques of US elastography. MATERIAL AND METHODS: Patients …were contacted who had undergone an implant replacement due to capsular contracture. Inclusion criterion was the re-implantation of a PU-coated implant. In the third year after changing the implant a follow-up examination was performed in 16 patients with 23 implants. A conventional examination with anamnesis, tactile and visual findings to obtain a Baker score, and ultrasound examinations including shear wave elastography, ARFI and compound elastography were performed. In addition, pain was evaluated using a visual analogue scale (VAS). RESULTS: The pain data showed a significant improvement (before implant exchange: 4.1±2.8 score points) with significance in favor of the current state (1.7±1.0 pain score points; p  = 0.002). All patients suffered from less or no pain three years after exchange of the implant. Pain values and elastography (ARFI values) correlated well (r  = 0,873), with increasing Baker score the ARFI values increased. US elastography evaluations can locally determine tissue density but correlate only to a limited extent with the test findings according to Baker. US elastography values of mammary gland tissue without implant did not differ from mammary gland tissue around implants. CONCLUSION: Preoperative Baker scores prior to exchange and the current Baker scores at the follow-up showed significantly lower score points three years after exchange of the implants. Ultrasound elastography seems to be an objective classification of capsular fibrosis. These first results motivate to initiate a prospective multicenter investigation. Show more

Keywords: Capsular fibrosis, ultrasound examinations, elastography, ARFI, Baker score

DOI: 10.3233/CH-200875

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

Authors: Park, Seong Jun | Yoon, Jung | Seo, Hong Seog | Lim, Chae Seung

Article Type: Research Article

Abstract: BACKGROUND: Platelet function analysis is crucial in assessing the hemostatic status to evaluate congenital and acquired platelet function defects. The Anysis-200 analyzer is a new automated lab-on-a-chip-based platelet function analyzer. OBJECTIVE: We aimed to evaluate a new platelet function analyzing system, the Anysis-200 in comparison to the Platelet Function Analyzer (PFA)-200 in cardiac patients. METHODS: Citrated blood was collected from 174 patients who visited the Department of Cardiology. The Anysis-200 consists of two kits, the microchips with collagen and epinephrine-coated membrane (C/EPI) or adenosine diphosphate-coated membrane (C/ADP). Platelet clogging in the Anysis-200 is measured by the …blood migration distance obtained by a camera, which is compatible with the closure time in the PFA-200. We performed Anysis-200 and PFA-200 analyzers simultaneously and compared the results. RESULTS: The sensitivity and specificity of the Anysis-200 C/EPI kit in comparison to the PFA-200 C/EPI kit were 63.41% and 91.43%, respectively. Regarding the C/ADP kit, the sensitivity and specificity of the Anysis-200 were 58.97% and 74.29%, respectively. The agreement rate between the Anysis-200 and PFA-200 for C/EPI was 83.35% and 70.14% for C/ADP. CONCLUSIONS: The Anysis-200, which applies a novel method to detect platelet clogging, has shown moderate to fair agreement with the PFA-200. This test is potentially useful for screening cardiac patients with an abnormal platelet function. Show more

Keywords: Platelet function, Anysis-200 analyzer, PFA-200 analyzer

DOI: 10.3233/CH-190801

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

Authors: Carlisi, Melania | Mancuso, Salvatrice | Caimi, Gregorio | Siragusa, Sergio

Article Type: Research Article

Abstract: The complement system is an essential component of the innate immune defence that, if overly activated, may damage organs and tissues. For this reason, there is a fine complement regulatory system. The complement modulation system includes two proteins with important regulatory activity, CD55 or decay accelerating factor (DAF) and CD59 or membrane inhibitor of reactive lysis (MIRL). The paroxysmal nocturnal hemoglobinuria (PNH) is a clonal and non-neoplastic disease characterized by intravascular haemolysis, occurrence of thrombosis and bone marrow failure. In clinical practice, in opposition to PNH, a variety of pathological conditions have been observed with an acquired and …non-genetic deficiency of the regulatory proteins CD55 and CD59. This abnormal, non-clonal, reduced expression of complement regulatory proteins configures what we may define as PNH-like phenotype. Similarly to PNH, even in the PNH-like phenotype diseases there has been a greater exposure to the mediated complement cellular lysis and, a likely increased risk of thromboembolic events. Therefore, the knowledge of the potential roles of the complement system becomes necessary for a deeper understanding of several pathological conditions and for an improved clinical management of the patients. Show more

Keywords: Paroxysmal nocturnal hemoglobinuria, complement system, CD55, CD59, thromboembolic risk

DOI: 10.3233/CH-190735

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2020

Authors: Zhang, Guang | Zhang, Tao | Sun, Xiubin | Tang, Fang | Lin, Haiyan | Liu, Yanxun | Zhang, Chengqi | Xue, Fuzhong

Article Type: Research Article

Abstract: The association between whole blood viscosity (WBV) and metabolic syndrome (MetS) is still scarcely investigated in the population-based prospective cohort. We aim to explore the longitudinal effect of WBV on MetS, and to verify whether WBV measures can be used as early predictors for MetS. The longitudinal cohort consisted of 3,508 adults (2,350 males and 1,158 females) who visited the health check-up system twice. WBV were measured at four shear rate (200, 50, 10 and 1 s-1 ), and their values were classified into quartiles. Multivariate Cox models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence …intervals (CIs) in men and women, respectively. A total of 444 (12.66%) incident MetS were observed at follow-up period. The incidences of MetS significantly increased with increasing quartiles of WBVs at all of the shear rate in men. After adjusting for baseline age, smoking, obesity, hypertension, hyperglycemia, and hyperlipidemia status, all of the WBV measures were significantly associated with incident MetS in men, and the HRs showed clear increasing trend across the quartiles of baseline WBVs. There were no significant association between WBVs and incident MetS in women. These findings suggest that MetS has a hemodynamic basis, and WBVs could be used as independent early predictor for MetS in men. Show more

Keywords: Whole blood viscosity, metabolic syndrome, prospective cohort

DOI: 10.3233/CH-15120

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Liu, Haifang | Zhu, Yuping | Jiao, Jie | Yuan, Jia | Pu, Tianning | Yong, Qiang

Article Type: Research Article

Abstract: The aim of this study was to assess the elasticity of Hashimoto’s thyroiditis in the different processes via supersonic ShearWave™ Elastography (SWE™). Quantitative information is delivered as Young’s modulus value expressed in kilo-Pascal (kPa). 30 healthy female and 30 healthy male individuals aging at 40±20 y had undergone conventional ultrasonography and SWE to determine the influence of gender on elasticity of thyroid. Also 60 female and 60 male patients (mean age, 40±20 y) with Hashimoto’s thyroiditis in different processes underwent conventional ultrasonography and SWE to determine the elasticity of thyroid in Hashimoto’s thyroiditis. Furthermore, the relationship between elasticity values and …thyroid peroxidase antibody (TPOAB) in the patients was investigated. We found significant impact of gender on elasticity values of healthy thyroids. Our study showed that increased elasticity values with statistical significance in hyperthyroidism stage, normal thyroid function stage and hypothyroidism were shown. Low degree relationship between elasticity values and TPOAB was found in 60 male patients. However, there was no such correlation in female patients. Show more

Keywords: ShearWave™ elastography, hashimoto’s thyroiditis, ultrasound imaging, elasticity

DOI: 10.3233/CH-170347

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2018