Clinical Hemorheology and Microcirculation - Volume 73, issue 2

Authors: Peng, Shiyun | Ding, Hong | Fu, Tiantian | Wang, Bengang | Wang, Wenping | Zhou, Jinzhu

Article Type: Research Article

Abstract: BACKGROUND: Savitzky-Golay filter is a digital filter used in data smoothing, we introduced a contrast-enhanced ultrasound (CEUS) quantification software based on the filter (SGCQ). OBJECTIVE: To explore the methodology of analyzing hepatic tumors hemodynamics applying SGCQ software and the correlation between SGCQ parameters and hepatocellular carcinoma (HCC) angiogenesis. METHODS: Nighty-seven right-lobe located hepatic mass cases (15 females and 82 males, mean age 58±10y, mean lesion size: 39.9±11.6 mm) underwent CEUS scan preoperatively and had a final diagnosis of HCC (n  = 52) or colorectal cancer metastatic liver tumors (MLT, n  = 45) were included. CEUS was carried out using …a 1–5 MHz convex probe. The CEUS clips were recorded and analyzed off-line to obtain the parameters. The parameters were analyzed by 3 observers separately to investigate inter-observer variability. Parameters were compared between tumor and adjacent liver and between different tumors. Immunohistochemistry was used to evaluate the microvessel density (MVD) of HCC, and the correlation between the parameters and MVD was analyzed. RESULTS: Intraclass correlation coefficient (ICC) of all parameters were greater than 0.75 except wash-in slope (a3) and time to peak (TTP) of adjacent liver. The parameters of a3, wash-out slope (a2), perfusion time (PT) and area under the curve (AUC) were significantly different between HCC and liver. The a2, a3, AUC, PT and enhanced intensity (EI) were significantly different between MLT and liver. AUC, a2, a3, da1 and dPI were significantly different between HCC and MLT. AUC, a2 and EI correlated with MVD. CONCLUSION: SGCQ software quantification have good consistency among three observers, the parameters of SGCQ can display the hemodynamics of HCC and MLT and the difference between them. AUC and EI can serve as useful biomarkers in tumor angiogenesis evaluation. Show more

Keywords: Contrast-enhanced ultrasound, Savitzky-Golay filter, methodology, hepatocellular carcinoma, colorectal cancer, neovascularization

DOI: 10.3233/CH-180432

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 271-282, 2019

Authors: Shin, Eun-Seok | Chung, Ju-Hyun | Park, Seung Gu | Saleh, Ahmed | Lam, Yat-Yin | Bhak, Jong | Jung, Friedrich | Morita, Sumio | Brachmann, Johannes

Article Type: Research Article

Abstract: BACKGROUND: Exercise electrocardiography (ECG) is frequently used as a diagnostic measure in patients with suspected coronary artery disease (CAD). However, it has low sensitivity for the detection of CAD. Magnetocardiography (MCG) has been proposed as an alternative tool to accurately diagnose CAD. OBJECTIVE: To date, a direct comparison of MCG to ECG has not been performed. This study sought to compare them for predicting the presence of significantly obstructive CAD. METHODS: The patients with chest pain or other symptoms suggestive of CAD were enrolled in the analysis. All the patients underwent a clinical evaluation, exercise ECG, …MCG test, and coronary angiography (CA). CAD was defined as stenosis ≥70% in at least one major coronary artery on quantitative analysis of CA. RESULTS: We prospectively enrolled 202 consecutive patients who suggested CAD. The prevalence of CAD on CA was 39.1%. Sensitivity and accuracy for CAD diagnosis was higher for MCG compared with exercise ECG (sensitivities 68.4% and 40.5%, p <0.001, specificities 95.1% and 91.1%, p = 0.267, and accuracies 84.7% and 71.3%, p <0.001, respectively). There was no incremental diagnostic value of combined MCG and ECG to detect coronary artery disease (p = 0.357). CONCLUSIONS: For the patients with intermediate to high risk of CAD, MCG exercise test provides better diagnostic accuracy for the detection of relevant obstruction of the epicardial coronaries when directly compared to exercise ECG. Show more

Keywords: Electrocardiography, magnetocardiography, diagnostic performance

DOI: 10.3233/CH-180485

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 283-291, 2019

Authors: Liu, Shui-Qing | Xie, Xiao | Liu, Yan-Ping | Ma, Yi-Bo | Zhang, Ling | Ge, Hong-Wei | Ding, Jiu-Le | Xing, Xiao-Xiao

Article Type: Research Article

Abstract:  Uterine arteriovenous malformation (AVM) is an extremely rare condition characterized by abnormal connections between veins and arteries. The atypical clinical manifestations and relatively low morbidity of AVM are conducive to missed diagnosis. The present study describes a case of a 47-year-old female patient with congenital uterine AVM followed by iatrogenic AVM. The diagnosis was established by contrast-enhanced ultrasound combined with contrast-enhanced CT (CECT). Because the symptom of vaginal bleeding was severe, trophoblastic disease or neoplasia could be preferred. The manifestations on various imaging examinations were carefully assessed, and the relevant literature was also reviewed.

Keywords: Uterine arteriovenous malformation, contrast-enhanced ultrasound, contrast-enhanced computed tomography, conventional ultrasound

DOI: 10.3233/CH-180489

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 293-298, 2019

Authors: Yang, Yancheng | Che, Yuanyuan | Yang, Likun

Article Type: Research Article

Abstract: OBJECTIVE: To analyze the relationship of the serum levels of inflammatory cytokines with the degree of anemia and vascular endothelial function in children with systemic lupus erythematosus (SLE), as well as to explore the predictive value of risk factors for SLE in children. METHODS: A total of 88 patients with SLE diagnosed in the Pediatric Department of our hospital from March 2015 to February 2017 were selected as the observation group, and 30 healthy controls with comparable age were selected as the control group. Basic characteristics of all enrolled individuals, such as age, sex, height and weight, and …the related biochemical indexes, including the levels of inflammatory cytokines [C-reactive protein (CRP), tumor necrosis factor α (TNF-α ), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR)], blood routine test including hemoglobin (Hb), platelet (PLT) and mean corpuscular volume as well as related indexes of vascular endothelial function, such as homocysteine (Hcy), carbonic oxide (NO), endothelial nitric oxide synthase (eNOS) were measured. In addition, the SLE disease activity index (SLEDAI) score of patients was also recorded. RESULTS: There were no significant differences regarding age, sex, body mass index (BMI), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) between observation group and control group (p  > 0.05), but the total cholesterol (TC) level in observation group was significantly higher than that in control group (p  < 0.05). In addition, the levels of CRP, TNF-α , IL-6 and ESR in serum in observation group were significantly higher than those in control group (p  < 0.05). However, the Hb, PLT and mean corpuscular volume in observation group were significantly lower than those in control group (p  < 0.05). Moreover, the levels of Hcy, NO and eNOS in observation group were significantly higher than those in control group (p  < 0.05). Furthermore, correlation analyses showed that CRP was positively correlated with SLEDAI score (r  = 0.791, p  < 0.001) and Hcy level (r  = 0.817, p  < 0.001), but negatively correlated with Hb level (r  = –0.663, p  < 0.001). CONCLUSION: There is a close relationship between serum inflammatory cytokines and SLE severity, Hcy or Hb level in children, suggesting these inflammatory cytokines might be novel indicators for evaluating the severity of SLE. Show more

Keywords: Children, systemic lupus erythematosus, inflammatory cytokine, anemia, vascular endothelial function

DOI: 10.3233/CH-180492

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 299-306, 2019

Authors: Han, Hong | Ji, Zhengbiao | Ding, Hong | Zhang, Weibin | Zhang, Ronghui | Wang, Wenping

Article Type: Research Article

Abstract: PURPOSE: To evaluate micro-flow imaging (MFI) in depicting the vascular architecture of hepatocellular carcinoma (HCC) and other focal liver lesions. MATERIALS AND METHODS: A total of 81 hepatic lesions were enrolled in this study. Each patient underwent CDFI, MFI, and CEUS examinations. The blood flow was first graded into three types (grade 1, 2 and 3) based on its richness with Adeler classification method. The differences in the grade of blood flow in liver tumors were compared between CDFI and MFI. With respect to the presented morphology, the blood flow was further classified into five types (Type I, …II, III, IV and V). The morphological differences in blood flow shown by MFI between malignant and benign hepatic tumors were then analyzed. RESULTS: For the total 81 lesions, MFI detected 61 lesion cases (75.31%) with blood flow grade 2 and 3, which obviously outperformed CDFI which detected 28 cases (34.57%) of grade 2 and 3 (χ 2 = 35.27, P  = 0.000). The MFI also showed that the most common blood flow morphology of HCC is Type-III (21/48, 43.75%) while the hepatic hemangioma (HEM) is mostly presented as Type V (5/10, 50%). Moreover, the grade of blood flow in MFI varied with different pathological subtypes of HCC (χ 2 = 5.610, P  = 0.018). CONCLUSIONS: Compared with traditional CDFI, MFI reveals more blood vessels in liver lesions with clearer view of blood flow distribution. Besides, MFI technology can demonstrate grade of blood flow for various differentiation stages of malignant liver tumors. Show more

Keywords: Micro-flow imaging (MFI), liver, tumor, vascular, color Doppler flow imaging

DOI: 10.3233/CH-180532

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 307-316, 2019

Authors: Kremer, Antje | Wußmann, Maximiliane | Herrmann, Marietta | Raghunath, Michael | Walles, Heike

Article Type: Research Article

Abstract: BACKGROUND: Prolyl hydroxylase inhibitors (PHIs) are promising compounds to promote angiogenesis by stabilizing hypoxia-inducible factor-1α (HIF-1α ), a master regulator of angiogenesis. Increased HIF-1α presence induces expression of proangiogenic genes such as vascular endothelial growth factor (VEGF). OBJECTIVE: We investigated the pharmacological induction of hypoxia via the PHI ciclopirox olamine (CPX) as angiogenesis strategy on human dermal microvascular endothelial cell (hd-mvEC) spheroids directly and indirectly via activating human mesenchymal stem cells (hMSCs). METHODS: HMSCs were isolated from bone marrow and hd-mvECs from foreskin biopsies. MSC-conditioned medium after CPX stimulation (MSC-CM CPX) was analyzed by …VEGF ELISA and Proteome Profiler™ Human Angiogenesis Array. Direct stimulation with CPX and indirect stimulation via MSC-CM CPX were compared in sprouting assays of hd-mvEC spheroids. RESULTS: Direct stimulation with CPX significantly increased sprouting of hd-mvEC spheroids. MSC-CM CPX also induced sprouting from hd-mvEC spheroids, which was mediated by angiogenic VEGF and other proangiogenic factors that had been produced by stimulated hMSCs. CONCLUSIONS: The stimulation with CPX increased the proangiogenic response of hd-mvECs and hMSCs. The direct stimulation of hd-mvECs with CPX has the potential to replace external VEGF supplementation. Thus, CPX can induce angiogenesis in ECs even in the absence of auxiliary cells demonstrating a promising proangiogenic approach. Show more

Keywords: HIF-1α, prolyl hydroxylase inhibitor, ciclopirox olamine, mesenchymal stem cells, endothelial cells, sprouting, angiogenesis, vascularization

DOI: 10.3233/CH-190559

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 317-328, 2019

Authors: Astapenko, David | Turek, Zdenek | Dostal, Pavel | Hyspler, Radomir | Ticha, Alena | Kaska, Milan | Zadak, Zdenek | Skulec, Roman | Lehmann, Christian | Cerny, Vladimir

Article Type: Research Article

Abstract: BACKGROUND: Endothelial glycocalyx (EG) is a carbohydrate-rich vascular lining of the apical surface of endothelial cells. It has been proved to have an essential role in vascular homeostasis. Lipid emulsions as part of parenteral nutrition (PN) are widely used in patients in the setting of critical care and perioperative medicine. Due to their structure, lipids may potentially interact with EG. The aim of the study was to evaluate the effect of lipid emulsion on EG. OBJECTIVE: To assess the influence of lipid emulsion on EG integrity in ICU patients using a videomicroscopic and biochemical methods. METHODS: …Patients in surgical ICU after major abdominal surgery or cardio surgery and in general ICU were assessed for eligibility for this pilot observational study in University Hospital. The study was performed during the first day of adding lipids as a part of their PN. The patients were given the SMOFlipid 20% for 6 hours in prescribed dose of approx. 1 g/kg of body weight. EG integrity was measured indirectly by automated sublingual videomicroscopy calculating a parameter PBR which describes the amount of lateral deviation of red blood cells from the central column and by levels of syndecan-1 and syndecan-4 in plasma as EG degradational products. Measurements were performed before lipid administration (T0) and 30 minutes after (T6) the infusion of lipid emulsion was completed. The statistical analysis was performed at the level of significance p  < 0.05, data are expressed as mean ± standard deviation (SD) and for PBR as median and interquartile range (IQR). RESULTS: Fifteen patients were studied, from them 9 included in final analysis. PBR (expressed in μ m) increased after the lipid infusion with no statistical significance (T0 = 2.10; 1.97–2.33 vs. 2.28; 2.11–2.45, p  = 0.13). At T6 both syndecans showed statistically significant decrease in their particular levels. Syndecan–1 at T0 = 2580±1013 ng/l, resp. at T6 = 2365±1077 ng/l, p  = 0.02; syndecan–4 at T0 = 134±29 ng/l, resp. at T6 = 123±43 ng/l, p  = 0.04. CONCLUSION: In our study, we showed that six hours long SMOFlipid 20% infusion had no detrimental effect on the EG integrity as assessed by PBR value and by syndecan-1 and syndecan-4 plasmatic levels. Observed decrease of syndecans shortly after lipid infusion allows us to hypothesize even possibly protecting effect of lipids on EG. Show more

Keywords: Endothelial glycocalyx, lipid emulsion, syndecan-1, syndecan-4, perfused boundary region, critically ill

DOI: 10.3233/CH-190564

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 329-339, 2019

Authors: Martini, Romeo

Article Type: Research Article

Abstract: Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial disease. It is clinically defined as rest pain with or without skin ulcer or gangrene and carries a very poor prognosis with a high rates of limb amputation and cardiovascular mortality. Despite the first definition of CLI has been published more than 30 years ago, the debate about what it really is, is still open. Over the years the hemodynamic parameters utilised to define the critical level of limb perfusion have changed. This has raised some question about the apparent confusion about the definition of CLI. Moreover, a …new term such as “limb threatening ischemia” has replaced the definition of CLI in recent guideline. Therefore, it becomes necessary to understand the evolution of the concept and the definition of CLI, to interpret the future trend. Hence, this work analysing the guideline documents on peripheral arterial disease that have defined the CLI to date, aims to clarify the path that has brought to the current conceptual changes of the definition of CLI. Show more

Keywords: Critical limb ischemia, limb amputation, risk chronic limb threatening ischemia

DOI: 10.3233/CH-190576

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 341-346, 2019

Authors: Lerchbaumer, Markus Herbert | Auer, Timo Alexander | Marticorena, Garcia Stephan | Stephan, Carsten | Hamm, Bernd | Jung, Ernst-Michael | Fischer, Thomas

Article Type: Research Article

Abstract: BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique in order to clarify testicular findings. CEUS is easy and fast to perform, overcomes the limitations of B-mode US. OBJECTIVE: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the assessment of unclear testicular pathologies. METHODS: CEUS examinations of 45 patients with unclear testicular pathologies between 2012 and 2018 were analyzed retrospectively. Examinations were performed using B-mode, colour Doppler (CCDS) and CEUS after injection of contrast agent (SonoVue® , Bracco) and interpreted by an experienced radiologist (EFSUMB level 3). Reference standard was defined …as histopathological report and clinical course. RESULTS: Overall 19 patients presented with a neoplastic lesion, whereas 14 were malignant. Matched to the histopathological report and clinical follow up, CEUS represented a sensitivity of 93% (95% -CI, 69–99), a specificity of 94% (95% -CI, 80–98), a positive predictive value (PPV) of 87% (95% -CI, 62–96) and a negative predictive value (NPV) of 97% (95% -CI, 83–99). CONCLUSION: CEUS is an accurate additional tool to differentiate between testicular alterations when B-mode US and CCDS are uncertain. CEUS may provide additional information and detect early enhancement in small tumor lesions when CCDS comes to its limit. Show more

Keywords: Contrast-enhanced ultrasound, CEUS, testis, testicular pathology

DOI: 10.3233/CH-190579

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 347-357, 2019

Authors: Ezer, Erzsebet | Schrick, Diana | Tőkés-Füzesi, Margit | Szapary, Laszlo | Bogar, Lajos | Molnar, Tihamer

Article Type: Research Article

Abstract: BACKGROUND: Elevated mean platelet volume (MPV) and immature platelet fraction (IPF) are predictive for vascular risk. Both can be associated with residual platelet reactivity. We aimed to explore associations among platelet characteristics and responder status in stroke patients on clopidogrel. METHODS: Blood samples from 46 patients and 15 healthy subjects were analyzed for platelet count, MPV, IPF, large cell ratio (LCR) and high-fluorsecent immature platelet fraction (H-IPF). As a novelty, not only whole blood, but upper and lower half blood samples after 1-hour gravity sedimentation were analyzed. Platelet aggregometry was used for the whole blood and separated samples …to explore area under the curve (AUC) in patients and controls. RESULTS: The AUC of the whole blood showed significant differences compared to the upper and lower samples separated after 1-hour sedimentation in patients and controls (p  < 0.001 and p  = 0.005 respectively). Remarkably, AUC measured in the upper samples in 59% of patients on clopidogrel were exceeding the therapeutic range suggesting that ascending platelets exert aggregation in the presence of ADP. This observation was associated with increased MPV and LCR in the upper samples (both p  = 0.04). Patients on clopidogrel were characterized as responders and non-responders and the percentage of H-IPF was significantly higher among non-responders compared to controls in the upper samples (p  = 0.04). CONCLUSIONS: The modified platelet function test may help to stratify patients with high residual platelet reactivity. Show more

Keywords: Immature platelet, clopidogrel, aggregometry, ischemic stroke

DOI: 10.3233/CH-190580

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 359-369, 2019

Authors: Geyer, Beatrice | Poch, Franz G. M. | Gemeinhardt, Ole | Neizert, Christina A. | Niehues, Stefan M. | Vahldiek, Janis L. | Klopfleisch, Robert | Lehmann, Kai S.

Article Type: Research Article

Abstract: BACKGROUND: Animal liver is established as an ex vivo model for studies on hepatic microwave ablation (MWA). Macroscopically visible color changes in the ablation zone are used to assess cell destruction and confirm successful ablation ex vivo . OBJECTIVE: Macroscopy and histology of MWA zones regarding cell viability in ex vivo porcine livers were compared in this study. METHODS: Six MWA were performed in porcine livers post mortem. A 14-G antenna and microwave generator (928 MHz; 9.0 kJ) were used. MWA were cut at the maximum cross section in vertical alignment to the antenna. NADH-diaphorase staining …determined cell vitality. Macroscopic and microscopic ablation zones were statistically analyzed. RESULTS: Histology showed two distinct ablation zones: central white zone (WZH) with no cell viability and peripheral red zone (RZH) with partial cell viability. However, the macroscopically visible WZM was significantly smaller than the microscopic WZH with an area difference of 43.1% (p  < 0.05) and a radius difference of 21.2% (1.6 mm; p  < 0.05). Macroscopy and histology showed a very high correlation for the complete lesion area (WZH/M+RZH/M; r  = 0.9; p  = 0.001). CONCLUSIONS: The avital central zone is significantly larger as the macroscopically visible WZ which is commonly used to assess successful ablation in MWA ex vivo studies. Irreversible cell destruction can be underestimated in macroscopic evaluation. Show more

Keywords: Liver, ex vivo, animal model, microwave ablation (MWA), viability staining, NADH-diaphorase

DOI: 10.3233/CH-190583

Citation: Clinical Hemorheology and Microcirculation, vol. 73, no. 2, pp. 371-378, 2019