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

Authors: Magyar, Zsuzsanna | Molnar, Abel | Nachmias, David Belkin | Mann, Din | Sogor, Viktoria | Mester, Anita | Peto, Katalin | Nemeth, Norbert

Article Type: Research Article

Abstract: BACKGROUND: Flap hypoperfusion or ischemia-reperfusion (I/R) may occur during preparation-transposition procedures and by postoperative thrombotic complications. Behind the microcirculatory disturbances micro-rheological alterations are also supposed. OBJECTIVE: We aimed to investigate the groin flap I/R with following-up micro-rheological parameters. METHODS: Anesthetized rats were subjected to Control or I/R groups. Groin flaps were prepared bilaterally, pedicled on the superficial epigastric vessels. In Control group the flaps were re-sutured after one hour, while in I/R group microvascular clips were applied on the pedicles for 60 minutes, then the flaps were repositioned. Besides daily wound control, before the operation …and on the 1st, 3rd, 5th, 7th and 14th postoperative days blood samples were collected for testing red blood cell (RBC) deformability (rotational ektacytometry) and aggregation (light-transmission aggregometry). RESULTS: RBC deformability significantly worsened by the 3rd–7th postoperative day in I/R group. RBC aggregation enhanced significantly by the 1st day, in I/R group it remained elevated on the 3rd day as well. In a complicated case with unilateral flap necrosis, RBC deformability and aggregation worsening was outlined from its group (base, 1st, 3rd day). CONCLUSION: Wound healing affected micro-rheological parameters in the early postoperative period. Flap I/R exacerbated the alterations. The parameters markedly worsened in case of flap necrosis. Show more

Keywords: Ischemia, microcirculation, hemorheology

DOI: 10.3233/CH-170277

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2017

Authors: Taeger, Christian D. | Friedrich, Oliver | Horch, Raymund E. | Drechsler, Caroline | Weigand, Annika | Hopf, Fabio | Geppert, Carol I. | Münch, Frank | Birkholz, Torsten | Wenzel, Carina | Geis, Sebastian | Prantl, Lukas | Buchholz, Rainer | Präbst, Konstantin

Article Type: Research Article

Abstract: BACKGROUND: Extracorporeal perfusion (EP) is moving into focus of research in reconstructive and transplantation medicine for the preservation of amputates and free tissue transplants. The idea behind EP is the reduction of ischemia-related cell damage between separation from blood circulation and reanastomosis of the transplant. Most experimental approaches are based on a complex system that moves the perfusate in a circular course. OBJECTIVE AND METHODS: In this study, we aimed to evaluate if a simple perfusion by an infusion bag filled with an electrolyte solution can provide acceptable results in terms of flow stability, oxygen supply and …viability conservation for EP of a muscle transplant. The results are compared to muscles perfused with a pump system as well as muscles stored under ischemic conditions with a one-time intravasal flushing with Jonosteril. RESULTS: With this simple method a sufficient oxygen supply could be achieved and functionality could be maintained between 3.35 times and 4.60 times longer compared to the control group. Annexin V positive nuclei, indicating apoptosis, increased by 9.7% in the perfused group compared to 24.4% in the control group. CONCLUSIONS: Overall, by decreasing the complexity of the system, EP by one-way infusion can become more feasible in clinical situations. Show more

Keywords: Extracorporeal perfusion, external field stimulation, free flap perfusion, reperfusion, ischemia, free flap transplantation

DOI: 10.3233/CH-170298

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2017

Authors: Di Stolfo, Giuseppe | Mastroianno, Sandra | Ruggieri, Maurizio | Fontana, Andrea | Marinucci, Roberto | Copetti, Massimiliano | Minervini, Maria Marta | Savino, Lucia | Mastroianno, Mario | Savino, Maria | Pacilli, Michele Antonio | Di Mauro, Lazzaro | Potenza, Domenico Rosario | Cascavilla, Nicola | Paroni, Giovanni | Russo, Aldo

Article Type: Research Article

Abstract: BACKGROUND: Carotid stenting stimulates intimal proliferation through platelet and stem cell activation. OBJECTIVE: The aim of this study is to evaluate whether the administration before or after carotid stenting of clopidogrel loading dose may play a role on circulating endothelial progenitor cells, stromal cell-derived factor-1α (SDF-1α ) and neointimal hyperplasia. METHODS: We recruited 13 patients (aged 74.52±7.23) with indication of carotid revascularization and in therapy with salicylic acid and statin. We blindly randomized them in two groups: pre-carotid angioplasty with stent (Pre-CAS group) receiving 300 mg of clopidogrel before stenting, and post-carotid angioplasty with stent (Post-CAS …group) receiving 300 mg after stenting. At the admission, we valued endothelial progenitor cells, SDF-1α and prospectively we repeated blood samples and measured intima-media thickness to estimate neointimal hyperplasia on the stent at 3, 6 and 12 months. RESULTS: In the days following the CAS, we found a lower, statistically not significant, trend of endothelial progenitor cells in Pre-CAS group. The SDF-1α concentration tended to be lower at baseline in the pre-CAS group than in the post-CAS group and it did not show an increase in the observed time. On the contrary, in the Post-CAS group we observed a peak at six hours with a significant reduction (p  <  0.001) at one day after stenting. The intima-media thickness was significantly lower in the Pre-CAS group than the Post-CAS group both at six months and 12 months after stenting. CONCLUSIONS: Pre-stenting clopidogrel loading dose leaded to short-time modification of endothelial progenitor cells and platelets and to long-term a minor neointimal hyperplasia. Show more

Keywords: Endothelial progenitor cells, intima-media thickness, carotid stenting, clopidogrel therapy

DOI: 10.3233/CH-180429

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2018

Authors: Shin, Eun-Seok | Chung, Ju-Hyun | Gu Park, Seung | 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, …a MCG exercise test, and coronary angiography (CA). CAD was defined as stenosis ≥70% stenosis 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. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Filar-Mierzwa, Katarzyna | Marchewka, Anna | Dąbrowski, Zbigniew | Bac, Aneta | Marchewka, Jakub

Article Type: Research Article

Abstract: OBJECTIVE: The aim of this study was to analyse the effects of dance movement therapy exercises (DMT) on the rheological properties of blood in elderly women. METHODS: The study encompassed group of women (mean aged: 67 years), who were subjected to three-month dance movement therapy programme (n  = 20). Blood samples from all the women were examined for their haematological, rheological, and biochemical parameters both prior to the study and three months thereafter. RESULTS: DMT did not cause statistically significant differences in the number of erythrocytes, thrombocytes, leukocytes and the haematocrit value. DMT affected …the rheological parameters of the blood in elderly women, improving the erythrocyte deformability at the lowest shear stress value and reducing the half-time of the total aggregation. Plasma viscosity and concentration of fibrinogen did not change after dance therapy. CONCLUSIONS: DMT modulate rheological properties of blood of older women. The results of this study suggest that physical exercise program for older women can prevent unfavorable age-related changes. Some indicators such as the haematological parameters, plasma viscosity and fibrinogen level were not affected by DMT in older women, suggesting the maintenance of homeostasis. Show more

Keywords: Dance movement therapy, elderly women, erythrocyte deformability, haemorheology, plasma viscosity

DOI: 10.3233/CH-180470

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Hahn, Robert G. | Hasselgren, Emma | Björne, Håkan | Zdolsek, Markus | Zdolsek, Joachim

Article Type: Research Article

Abstract: BACKGROUND: Injury (shedding) of the endothelial glycocalyx layer, which alters local blood flow and microvascular permeability, is assessed by measuring components of this layer in circulating blood. The influence of renal function on their concentrations is unknown. METHODS: Plasma and urine concentrations of three shedding products (syndecan-1, hyaluronic acid, and heparan sulfate) and creatinine were measured over 5 hours in 15 healthy volunteers and 15 postoperative patients; this guaranteed a spread of kidney functions. Renal clearances were calculated. RESULTS: Low renal clearances of syndecan-1 (mean 3.5 mL/min) and hyaluronic acid (0.8 mL/min) correlated inversely with the 6-fold variability …in the plasma concentrations of these substances (r  = – 0.45 and– 0.49). Low creatinine clearance correlated inversely (r  = – 0.60) and plasma creatinine directly (r  = 0.52) with the two-fold variability in heparan sulfate, which was the only shedding substance that also correlated with C-reactive protein (r  = 0.51) and, therefore, showed higher concentrations after surgery. CONCLUSIONS: The present explorative study suggests that a 6-fold variability in the plasma concentrations of three commonly measured endothelial shedding products can be understood by the kidney’s ability to excrete them. This finding has implications when interpreting results of studies where shedding is assessed. Show more

Keywords: Endothelial glycocalyx, syndecan-1, heparan sulfate, hyaluronic acid, kidney function, renal clearance

DOI: 10.3233/CH-180444

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

Authors: Lee, Chang Youn | Lee, Jiyun | Seo, Hyang-Hee | Shin, Sunhye | Kim, Sang Woo | Lee, Seahyoung | Lim, Soyeon | Hwang, Ki-Chul

Article Type: Research Article

Abstract: BACKGROUND: Cardiac hypertrophy is an important risk factor for heart failure. The MEK-ERK axis has been reported as a major regulator in controlling cardiac hypertrophy. TAK733 is a potent and selective MEK inhibitor that suppresses cell growth in a broad range of cell lines. OBJECTIVE: Therefore, we aimed to investigate the anti-hypertrophic effect of TAK733 in cardiomyocytes. METHODS: Cardiomyocyte hypertrophy was induced with norepinephrine (NE) or phenylepinephrine (PE) using H9c2 cells. To confirm the cardiomyocyte hypertrophy, cell size and protein synthesis were measured and hypertrophy-related gene expression was estimated by reverse transcription polymerase chain reaction. To …identify the signaling pathway involved, immunoblot analysis were performed. RESULTS: We observed that NE activated MEK-ERK signaling and increased ANP and BNP expression, resulting in cardiomyocyte hypertrophy. TAK733 significantly reduced cardiomyocyte hypertrophy by regulating NE-induced ERK1/2 and ERKThr188 activation, hypertrophy marker expression, and cardiomyocyte hypertrophy through depression of MEK activity. In addition, we examined that PE-induced cardiomyocyte hypertrophy was also attenuated by TAK733. CONCLUSIONS: Here, we report that TAK733 suppressed NE- or PE-induced cardiomyocyte hypertrophy by repressing a crucial component of cardiac hypertrophy-related pathways. These results suggest that TAK733 may be a useful therapeutics for cardiac hypertrophy and warrants further in vivo studies. Show more

Keywords: Cardiac hypertrophy, MEK inhibitor, TAK733, norepinephrine

DOI: 10.3233/CH-180476

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Bach, Annika | Hameister, Clarissa | Slowinski, Torsten | Jung, Ernst Michael | Thomas, Anke | Fischer, Thomas

Article Type: Research Article

Abstract: BACKGROUND: Besides mammography, breast ultrasound is the most important imaging modality for women with suspected breast cancer. New software tools bear high potential for improved detectability and specification of malignant breast lesions. OBJECTIVE: To compare the halo depicted around malignant breast lesions by ultrasound using Acoustic Structure Quantification (ASQ) of raw image data with the echogenic rim seen in B-mode ultrasound. METHODS: This retrospective study included 37 women for whom conventional B-mode ultrasound of the breast and ASQ were available as well as histopathology findings for comparison. Software tools were used to measure the halo area …or echogenic rim and tumor area and calculate halo-to-lesion ratios for the two ultrasound modes. Six inexperienced readers characterized the breast lesions based on this information. Specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. ANOVA, the Wilcoxon test, and ROC curve analysis were performed. RESULTS: There was a linear relationship between ASQ-based and B-mode-based halo-to-lesion ratios; however, a systematic error was also noted. ASQ-derived ratios tended to be higher for breast lesions with lymphangioinvasion (p  = 0.051, n.s.) and higher N-stages (p  > 0.925, n.s.), while there was no correlation with other markers. Because of the significantly greater conspicuity of peritumoral halos in the ASQ mode, inexperienced readers achieved greater sensitivity (78% vs. 74%) and specificity (75% vs. 71%) and higher NPVs (75% vs. 71%) and PPVs (78% vs. 74%) compared with B-mode images. Greater halo conspicuity affected the identification of malignant lesions with both modes; ASQ was found to be particularly well suited (FBimage (1,100) = 19.253, p  < 0.001; FASQ (1,100) = 52.338, p  < 0.001). The inexperienced readers were significantly more confident about their diagnosis using the ASQ maps (z = –3.023, p  = 0.003). CONCLUSIONS: We conclude that the halo in ASQ and the echogenic rim in B-mode ultrasound are attributable to different morphologic correlates. ASQ improves diagnostic accuracy and confidence of inexperienced examiners because of improved halo visibility. Show more

Keywords: Ultrasound, breast neoplasms, breast cancer, breast lesion, B mode, ASQ, sonography, diagnostic imaging, halo, peripheral rim, peripheral zone, BI-RADS

DOI: 10.3233/CH-180484

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Beral, Laurence | Romana, Marc | Lemonne, Nathalie | David, Thierry | Connes, Philippe

Article Type: Letter

DOI: 10.3233/CH-190552

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 2018

Authors: Zhang, Yi | Wu, Ruipeng | Gu, Cheng | Gao, Fulin | Hu, Xiaojuan | Dong, Tong | Zang, Peixi

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the role and potential mechanism of Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κ B) signaling pathway in cognitive impairment induced by cerebral small vascular disease (CSVD), so as to provide a reference for the clinical treatment of CSVD-induced cognitive impairment. METHODS: Mice with TLR4 gene knockout (n  = 20) and those with wild-type TLR4 gene (n  = 40) aged 8–10 weeks old were divided into blank control group (Control group, n  = 20), wild-type + CSVD group (WT + CSVD group, n  = 20) and TLR4 gene knockout + CSVD group (TLR4 KO + CSVD group, n  = 20). Allogeneic thrombosis (particle diameter: 50–70 mm) was injected …to the mouse’s external carotid artery to create a model of learning and memory dysfunction. Step-down test and Y-type maze test were utilized to examine the learning and memory abilities of the mice. Reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting techniques were adopted to measure the levels of apoptosis-related genes [B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (Bax), C-caspase-3 and T-caspase-3] in the brain tissues of mice. Terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method was applied to detect the apoptosis of neuronal cells in the brain tissues. Meanwhile, the levels of oxidative stress markers, including superoxide dismutase (SOD), gp91 and malondialdehyde (MDA), were measured. Finally, the expression level of TLR4/NF-κ B pathway was detected. RESULTS: The latency in the step-down test in the WT + CSVD group was remarkably longer than that in the Control group, and the number of errors was evidently larger than that in the Control group (p  <  0.05). At the same time, in the WT + CSVD group, the expression levels of pro-apoptotic genes Bax and C-caspase-3 were up-regulated markedly, while the expression level of anti-apoptotic gene Bcl-2 declined notably (p  <  0.05). TUNEL results showed that the number of apoptotic cells in the brain tissues in the WT + CSVD group was about 12 times that in the Control group (p  <  0.05). Meanwhile, the SOD expression level was lowered, and the MDA expression level was elevated in the brain tissues in the WT + CSVD group. In addition, the TLR4/NF-κ B pathway was prominently activated in the mice in the WT + CSVD group (p  <  0.05). After TLR4 gene knockout, the cognitive functions of the mice were improved markedly, and the apoptosis of neuronal cells and oxidative stress in the brain tissues were suppressed significantly in the meantime. Moreover, the activation of the TLR4/NF-κ B signaling pathway was also inhibited. CONCLUSION: The TLR4/NF-κ B pathway is involved in the occurrence and development of CSVD-induced cognitive impairment through regulating oxidative stress and cell apoptosis. Show more

Keywords: TLR4/NF-κB, CSVD, cognitive impairment

DOI: 10.3233/CH-180515

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Guo, Le-Hang | Li, Dan-Dan | Wang, Dan | Li, Xiao-Long | Liu, Bo-Ji | Chen, Shi-Gao | Xu, Hui-Xiong

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the stiffness distribution in the ablated zone after radiofrequency ablation (RFA), we used a device called tissue elastometer based on gross liver samples. MATERIALS: AND METHODS: Twelve freshly excised porcine livers were subject to RFA under a same setup to form elliptic ablated samples. Each sample was cut open for gross examination, and then the surface of the section plane was sliced into one piece for Young’s modulus test using the tissue elastometer. Five test points along the long- and short-axis on each piece were selected to evaluate stiffness distribution respectively. Among them, …four points distributed equidistantly from center to boundary in the ablated zone and one was in the unablated zone. RESULTS: In the ablated zone, we found the Young’s moduli were significantly different among the four test points both in long- (F = 99.04, p <0.001) and short-axis (F = 79.47, p <0.001) directions. The Young’s modulus showed a downtrend in each direction, and was linearly related to the distance from the center to the test point (for long axis, R2 = 0.968; for short axis, R2 = 0.984, both p <0.001). A more significant downtrend was observed in short-axis direction. The Young’s moduli gained from the inner edge of ablated zone were comparable and significantly higher than those from the outer edge for both directions. The maximum value of 24.71kPa for Young’s modulus was the appropriate threshold to ensure the tissues were necrotic completely. CONCLUSION: The stiffness inside the ablated zone represented a radial distribution with downtrend, following a linear law. The stiffness at the inner edge of ablated zone is stable and significantly higher than that at the outer edge. The maximum value of 24.71 kPa close to the inner edge of Wz may be used as the standard of complete ablation. Show more

Keywords: Stiffness distribution, Radiofrequency ablation, Tissue elastometer, Young’s modulus

DOI: 10.3233/CH-180404

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Renno, Isabell | Boos, Anja M. | Horch, Raymund E. | Ludolph, Ingo

Article Type: Research Article

Abstract: BACKGROUND: Negative pressure wound therapy applied over closed incisions (ciNPT) has been shown to influence wound healing. Therefore, the aim of this study was to examine the short-term effects of ciNPT on skin perfusion patterns in postbariatric wounds. METHODS: 17 patients were included. Patients from the study group received a ciNPT dressing with a continuous negative pressure of – 125 mmHg for five days. Two intra- and two postoperative measurements were performed using both a combined laser Doppler spectrophotometry and an ICG angiography system to determine oxygen saturation (sO2), hemoglobin content (rHb) and perfusion patterns. RESULTS: Three …days postoperatively the sO2 was significantly higher in the study group compared to the control group and also compared to the end of the operation. Concerning the rHb, there was no statistical significant alteration in or between the groups, but a trend towards a correlated alteration of sO2 and rHb. ICG angiography showed an earlier and stronger enhancement of perfusion parameters in the study group. CONCLUSION: CiNPT has a positive effect on oxygen saturation and tissue perfusion, which are both associated with the wound healing process. The use of ciNPT could therefore possibly reduce the risk of wound healing complications in this high-risk patient group. Show more

Keywords: Skin perfusion patterns, combined laser Doppler spectrophotometry, ICG angiography, oxygen saturation, relative hemoglobin content, wound healing, O2C, SPY, weight loss, obesity, maintenance of weight loss, body contouring surgery, abdominoplasty, postoperative complications, closed incisional negative pressure wound therapy, ciNPWT, ciNPT, NPWT, postbariatric surgery, postoperative wound care, high-risk patients

DOI: 10.3233/CH-180450

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Saha, Amit K. | Schmidt, Brendan R. | Wilhelmy, Julie | Nguyen, Vy | Abugherir, Abed | Do, Justin K. | Nemat-Gorgani, Mohsen | Davis, Ronald W. | Ramasubramanian, Anand K.

Article Type: Research Article

Abstract: BACKGROUND: Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a poorly understood disease. Amongst others symptoms, the disease is associated with profound fatigue, cognitive dysfunction, sleep abnormalities, and other symptoms that are made worse by physical or mental exertion. While the etiology of the disease is still debated, evidence suggests oxidative damage to immune and hematological systems as one of the pathophysiological mechanisms of the disease. Since red blood cells (RBCs) are well-known scavengers of oxidative stress, and are critical in microvascular perfusion and tissue oxygenation, we hypothesized that RBC deformability is adversely affected in ME/CFS. METHODS: We used a …custom microfluidic platform and high-speed microscopy to assess the difference in deformability of RBCs obtained from ME/CFS patients and age-matched healthy controls. RESULTS AND CONCLUSION: We observed from various measures of deformability that the RBCs isolated from ME/CFS patients were significantly stiffer than those from healthy controls. Our observations suggest that RBC transport through microcapillaries may explain, at least in part, the ME/CFS phenotype, and promises to be a novel first-pass diagnostic test. Show more

Keywords: Chronic Fatigue Syndrome, microfluidics, cell deformability, red blood cells

DOI: 10.3233/CH-180469

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-4, 2018

Authors: Georgieva, M. | Prantl, L. | Utpatel, K. | Wiesinger, I. | Stroszczynski, C. | Jung, F. | Jung, E.M.

Article Type: Research Article

Abstract: OBJECTIVE: Objective of the study was to assess the performance of ultrasound strain elastography combined with conventional B-mode ultrasound to diagnose suspicious breast lesions (BI-RADS 4 and 5). METHODS: Between January 2015 and December 2017, a total of 86 patients (55±17.9 years) with solid or unclear, non-cystic breast lesions were enrolled in the study. The breast lesions were evaluated by B-mode ultrasound and subsequent ultrasound strain elastography. Ultrasound features including echo pattern, lesion shape, marginal characteristics, calcifications, orientation and posterior features are useful for differentiating benign breast lesions from malignant ones. Malignant ultrasound features are irregular shape, hypoechoic …pattern, spiculated margin, nonparallel orientation and posterior shadowing. Lesions with benign features such a circumscribed margin were classified as low conspicuous. In patients with highly conspicuous malignant masses ultrasound-guided core needle biopsy or surgical excision was performed. RESULTS: Among the 86 patients, 60 masses were histologically proven and 36 of these were malignant. Of the malignant lesions 26 invasive carcinomas were of no special type (NST), 1 invasive lobular carcinoma, 3 ductal carcinomas in situ and 6 metastases. 20 of these patients had breast density classified as ACR 3 or 4. The mean size of the masses was 1.2 cm (range: 0.5–5 cm). Based on ultrasound B-mode imaging, the lesions were classified as BI-RADS category 4 (n  = 20; three 4a, nine 4b and eight 4c) and BI-RADS category 5 (n  = 16). One patient had to be reclassified after strain elastographxy to BI-RADS 3. The sensitivity of ultrasound with strain elastography and additional B-Mode ultrasound for the characterization of solid breast lesions was 97%, for conventional B-mode alone 92%; the respective specificities were 82% and 73%, respectively. CONCLUSION: Ultrasound elastography can be a supplementary approach to conventional ultrasound to improve the diagnostic accuracy of malignant breast lesions. Show more

Keywords: Breast lesions, ultrasound, elastography, breast imaging reporting and data system, invasive carcinoma of no special type (NST)

DOI: 10.3233/CH-189415

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Lee, Hoyoon | Na, Wonwhi | Lee, Byoung-Kwon | Lim, Chae-Seung | Shin, Sehyun

Article Type: Research Article

Abstract: The analysis of platelet aggregation and thrombosis kinetics has significantly advanced with progress in microfluidic technology. However, the results of platelet aggregation tests do not fully reflect the observed clinical outcomes. To address the present unmet clinical needs, the basic but essential biology of platelets should be reconsidered in relation to the characteristics of microfluidic systems employed for platelet tests. To this end, the present article provides an overview of commercially available point of care devices and focuses on recent microfluidic studies, describing their measurement principles. We critically discuss the characteristics of the microfluidics systems used to evaluate the complex …processes underlying platelet aggregation, and that are specifically designed to mimic the pathophysiological environment of blood vessels, including hemodynamic factors as well as blood vessel injury. To this end, we summarize unsolved issues related to the application of platelet function tests based on microfluidics. Overall, we confirm that platelet function tests based on microfluidics provide a versatile platform that encompasses a variety of basic research, as well as clinical diagnostic applications. Show more

Keywords: Platelets, function, test, microfluidic, diagnostic

DOI: 10.3233/CH-189416

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-19, 2018

Authors: Putz, Franz J. | Verloh, Niklas | Erlmeier, Anna | Schelker, Roland C. | Schreyer, Andreas G. | Hautmann, Matthias G. | Stroszczynski, Christian | Banas, Bernhard | Jung, Ernst M.

Article Type: Research Article

Abstract: AIM: To assess the influence of difficult examination conditions onto the diagnostic performance of CEUS (contrast-enhanced ultrasound) in focal liver lesions (FLL). METHODS: 77 liver CEUS examinations of 75 patients were analysed retrospectively. CEUS was performed as the first diagnostic procedure by one experienced sonographer after bolus injection of 1.0 up to 2.4 ml sulphur hexafluoride microbubbles using a high-end ultrasound device with a high resolution multifrequency probe (1–6 MHz). The combination of complementary imaging (CT or MRI), histology and CEUS follow up of at least 6 months was considered. Cross tables were used to define the sensitivity, specificity, positive …predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy. Chi-Square Test analysed categorical data. RESULTS: The patients were between 18 and 84 years old (mean 62±11 years). 26 patients suffered from liver cirrhosis (33.8% ). 52 patients (67.5% ) received therapy for an oncological disease. The final diagnosis showed 52 malignant FLLs including 24 hepatocellular carcinomas (HCCs), 9 cholangiocellular carcinomas (CCCs) and 19 metastases from different primary tumors. In the other 25 patients no malignant lesions could be detected, three of them presenting however liver haemangioma and two of them liver cysts. The overall lesions’ size according to the CEUS findings ranged from 7 to 100 mm (mean 31.1±22.6 mm). Under good examination conditions the malignant potential of a tumor was diagnosed correctly by CEUS in 98.0% of cases (Sensitivity 97.1%, Specificity 100%, PPV 100%, NPV 94.1%, diagnostic accuracy 98.0% ). Limited examination conditions (e.g. obesity, meteorism) were present in 35.1% of cases with a decrease of the diagnostic accuracy to 92.6% (Sensitivity 100%, Specificity 77.8%, PPV 90.0%, NPV 100% ). CONCLUSION: Despite the influence of difficult examination conditions, CEUS is – in the hands of an experienced sonographer – an excellent diagnostic procedure for the assessment of liver lesions. Show more

Keywords: CEUS, liver imaging, interdisciplinary ultrasound department, examination conditions, tumor

DOI: 10.3233/CH-189417

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Reinthaler, Markus | Johansson, Johan Bäckemo | Braune, Steffen | Al-Hindwan, Haitham Saleh Ali | Lendlein, Andreas | Jung, Friedrich

Article Type: Research Article

Abstract: Circulating blood cells are prone to varying flow conditions when contacting cardiovascular devices. For a profound understanding of the complex interplay between the blood components/cells and cardiovascular implant surfaces, testing under varying shear conditions is required. Here, we study the influence of arterial and venous shear conditions on the in vitro evaluation of the thrombogenicity of polymer-based implant materials. Medical grade poly(dimethyl siloxane) (PDMS), polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) films were included as reference materials. The polymers were exposed to whole blood from healthy humans. Blood was agitated orbitally at low (venous shear stress: 2.8 dyne · …cm–2 ) and high (arterial shear stress: 22.2 dyne · cm–2 ) agitation speeds in a well-plate based test system. Numbers of non-adherent platelets, platelet activation (P-Selectin positive platelets), platelet function (PFA100 closure times) and platelet adhesion (laser scanning microscopy (LSM)) were determined. Microscopic data and counting of the circulating cells revealed increasing numbers of material-surface adherent platelets with increasing agitation speed. Also, activation of the platelets was substantially increased when tested under the high shear conditions (P-Selectin levels, PFA-100 closure times). At low agitation speed, the platelet densities did not differ between the three materials. Tested at the high agitation speed, lowest platelet densities were observed on PDMS, intermediate levels on PET and highest on PTFE. While activation of the circulating platelets was affected by the implant surfaces in a similar manner, PFA closure times did not reflect this trend. Differences in the thrombogenicity of the studied polymers were more pronounced when tested at high agitation speed due to the induced shear stresses. Testing under varying shear stresses, thus, led to a different evaluation of the implant thrombogenicity, which emphasizes the need for testing under various flow conditions. Our data further confirmed earlier findings where the same reference implants were tested under static (and not dynamic) conditions and with fresh human platelet rich plasma instead of whole blood. This supports that the application of common reference materials may improve inter-study comparisons, even under varying test conditions. Show more

DOI: 10.3233/CH-189410

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Ahmed, M. | Lutze, S. | Tembulatow, M. | Daeschlein, G. | Jünger, M. | Arnold, A.

Article Type: Research Article

Abstract: BACKGROUND: Chronic venous disease (CVD) is extremely common worldwide with prevalence increasing with age. It is associated with a reduced quality of life, particularly in relation to pain, physical function and mobility. Symptomatic chronic venous insufficiency (CVI) with venous ulcer at its, endpoint, indicates interventional surgery to cure venous reflux therewith promoting wound healing and preventing recurrence. In this retrospective, single-centre, consecutive case-control study in a single patient population of a university clinic in northern Germany a holistic evaluation of varicose vein surgeries has been undertaken. Part I covered postoperative complications in relation to co-morbidities, co-medication and clinical presentation. Part …II of this article presents now the hemodynamic results in relation to the perioperative evolution of CVI specific symptoms. METHODS: Records of n  = 429 (467 extremities) patients from 2009-2013 treated with open surgery were analysed with regards to perioperative hemodynamics. Evolution of CVI symptomology was accessed postoperatively with the help of a questionnaire and patient records in the case of complication development. Venous hemodynamics was analysed in the whole patient population and with regards to complication subgroups: no events (NE), neglectable adverse events (NAE) and non-neglectable adverse events (NNAE). RESULTS: Postoperatively, patients CVI symptoms like pain (p  <  0.001), swelling (p  <  0.001) and itching (p  = 0.003) significantly improved. The venous refill time and venous pump capacity improved significantly after open vein surgery (p  <  0.05). Regardless of the development of postoperative complications there was a significant improvement of venous function at 6 weeks- and one year postoperative (p  <  0.05). Symptom regression was strongly correlated with hemodynamic improvement. CONCLUSION: A significant improvement of patients’ symptoms was achieved by means of open-surgery, regardless of postoperative complication development. This was in accordance with the improvement of venous hemodynamics. A strong correlation between symptom regression and improvement in venous hemodynamics could be proven. Show more

Keywords: Perioperative hemodynamics, perioperative symptomology, digital photoplethysmography

DOI: 10.3233/CH-189401

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Heine-Geldern, A. | Broer, P.N. | Prantl, L. | Brebant, V. | Anker, A.M. | Kehrer, A. | Thiha, A. | Lonic, D. | Ehrl, D. | Ninkovic, M. | Heidekrueger, P.I.

Article Type: Research Article

Abstract: BACKGROUND: While complication rates in free tissue transfers have continuously decreased over time due to improved techniques, the intraoperative use of vasopressors and their negative effects on flap microcirculation and patency of the anastomoses remains controversial. To further elucidate this matter, this retrospective study examines the effect of intraoperative vasopressors on free gracilis muscle and free fasciocutaneous anterolateral thigh (ALT) flaps for lower extremity reconstruction. METHODS: A total of 425 patients underwent 437 free flaps for lower limb reconstruction. The series was divided into two groups: use of intraoperative vasopressors (V, n  = 318) or no use (NV, n … = 119). The data were retrospectively screened for patients’ demographics, perioperative details, and surgical complications. RESULTS: The two groups were comparable regarding patient comorbidities. Independently of flap type, there were no significant difference between the groups regarding major complications, i.e. total flap loss (V: 5.35% versus NV: 5.04%, p  = 0.899) or revision rate (V: 18.87% versus NV: 12.61% ; p  = 0.122), or minor complications, i.e. partial flap loss (V: 6.29% versus NV: 5.88%, p  = 0.875). CONCLUSION: This study confirms that the usage of intraoperative vasopressors has no influence on free flap survival rate in lower extremity reconstruction. It seems to be no difference between free muscle or fasciocutaneous flaps. Show more

Keywords: Vasopressors, microsurgery, free flaps, norepinephrine, lower extremity reconstruction

DOI: 10.3233/CH-189411

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Varga, Gabor | Ghanem, Souleiman | Szabo, Balazs | Nagy, Kitti | Pal, Noemi | Tanczos, Bence | Somogyi, Viktoria | Barath, Barbara | Deak, Adam | Peto, Katalin | Nemeth, Norbert

Article Type: Research Article

Abstract: BACKGROUND: Pathomechanism and optimal renoprotective protocol for remote ischemic preconditioning (RIPC) have not been completely revealed yet. OBJECTIVE: To investigate micro-rheological effects of early and delayed RIPC in renal ischemia-reperfusion (I/R) in the rat. METHODS: In Control group the left femoral artery was cannulated and the left kidney was gently exposed. In the I/R group 45-minute renal ischemia with 120-minute reperfusion period was monitored. In the RIPC groups a 3×10-minute protocol was applied using tourniquet around the right hind-limb 1 hour (RIPC-1) or 24 hours (RIPC-24) prior to the I/R. Blood samples were taken for …testing blood gas, acid-base, metabolic and hemorheological parameters. RESULTS: Lactate and potassium concentration significantly increased in I/R that could be reduced by RIPC, especially in RIPC-24. Creatinine concentration increased further in RIPC groups. I/R and RIPC-1 decreased the pH, RIPC-24 increased. RIPC-24 reduced the drop in base excess. Erythrocyte deformability worsened by renal I/R. In RIPC groups deformability decreased additively. However, RIPC-1 could improve the condition. RIPC-24 showed the highest erythrocyte aggregation values during reperfusion. CONCLUSIONS: Renal I/R worsened metabolic and micro-rheological parameters that could be modulated by RIPC protocols. However, it could not be decided whether the early or the delayed protocol is better. Show more

Keywords: Ischemia-reperfusion, remote ischemic preconditioning, kidney, red blood cell deformability, red blood cell aggregation

DOI: 10.3233/CH-189414

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Chung, Ju-Hyun | Lee, Kyung Eun | Park, Jai-Wun | Shin, Eun-Seok

Article Type: Research Article

Abstract: While fractional flow reserve (FFR) is a good diagnostic index to assess the myocardial ischemia, coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) can be used to address microvascular status without any significant epicardial disease. The independent predictors of for FFR and IMR are totally different and acts differently on the macro- and micro-vascular dysfunction. In high FFR patients, low CFR and high IMR which indicates the presence of overt microvascular disease demonstrated poor prognosis. Thus, comprehensive physiological assessments using FFR, CFR and IMR could improve the ability to discriminate patients at high risk of future events.

Keywords: Microvascular dysfunction, fractional flow reserve, coronary flow reserve, index of microcirculatory resistance

DOI: 10.3233/CH-189403

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-4, 2018

Authors: Horobin, Jarod T. | Watanabe, Nobuo | Hakozaki, Masaya | Sabapathy, Surendran | Simmonds, Michael J.

Article Type: Research Article

Abstract: BACKGROUND: Red blood cells (RBC) are exposed to varying shear stress while traversing the circulatory system; this shear initiates RBC-derived nitric oxide (NO) production. OBJECTIVE: The current study investigated the effect of varying shear stress dose on RBC-derived NO production. METHODS: Separated RBC were prepared with the molecular probe, diamino-fluoreoscein diacetate, for fluorometric detection of NO. Prepared RBC were exposed to discrete magnitudes of shear stress (1–100 Pa), and intracellular and extracellular fluorescence was quantified via fluorescence microscopy at baseline (0 min) and discrete time-points (1–30 min). RESULTS: Intracellular RBC-derived NO fluorescence was significantly increased (p  < … 0.05) following shear stress exposure when compared to baseline at: i) 1 min–100 Pa; ii) 5 min–1, 5 Pa; iii) 15 min–1, 5, 35 Pa; iv) 30 min–35 Pa. Extracellular RBC-derived NO fluorescence was significantly increased (p  <  0.05) following shear stress exposure when compared to baseline at: i) 5 min – 100 Pa; ii) 15 min–100 Pa; iii) 30 min–40, 100 Pa. CONCLUSIONS: These data indicate that: i) a dose-response exists for the RBC-derived production of NO via shear stress; and ii) exposure to supra-physiological shear stress allows for the leakage of RBC intracellular contents (e.g., RBC-derived NO). Show more

Keywords: Haemorheology, erythrocyte, mechanotransduction, vasodilation, biocompatibility

DOI: 10.3233/CH-189412

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Mrowietz, C. | Franke, R.P. | Pindur, G. | Sternitzky, R. | Jung, F. | Wolf, U.

Article Type: Research Article

Abstract: BACKGROUND: The laser Doppler fluxmetry (LDF) is a non-invasive method to assess skin blood perfusion, measuring the flow of blood cells inside a tissue volume without harming the tissue. In the diagnosis of skin circulation disorders, the results of the LDF measurement are generally used in such a way that “normal” (or non-ill) or “pathological” values are achieved by comparison with a reference sample, for example of apparently healthy subjects. MATERIAL AND METHODS: In this study, the values of LDF for the diagnosis of microcirculatory disorders in patients with coronary artery disease (n  = 20) or in patients …with microcirculatory disorders, already diagnosed by capillary microscopy (n  = 46), were examined. RESULTS: The mean values of LD amplitudes in the four frequency windows for patients with coronary artery disease were in the reference range. However, some of the patients showed reduced LD values: in eleven of the twenty patients, one or more mean LD amplitudes were below the reference range. Four of the eleven patients had pathologically decreased capillary erythrocyte velocities of v ery  = 0.09–0.21 [mm/s], while the other seven patients had normal blood circulation at rest. For all patients with a proven cutaneous microcirculatory disorder, the mean LD amplitude in at least one of the frequency windows FF2 to FF4 was pathologically reduced. CONCLUSION: The Laser-Doppler fluxmetry method used in the study allows the reliable diagnosis of cutaneous microcirculatory disorders. Show more

Keywords: Laser-Doppler fluxmetry, cutaneous microcirculation, atherosclerosis

DOI: 10.3233/CH-189402

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Negrão de Figueiredo, G. | Mueller-Peltzer, K. | Armbruster, M. | Rübenthaler, J. | Clevert, D.A.

Article Type: Research Article

Abstract: BACKGROUND: The first method of choice for gallbladder alteration detection is the conventional ultrasound. Due to some imaging limitations, contrast-enhanced ultrasound (CEUS) has been widely used in the last years. CEUS is an additional modality that is able to depict microvessels flow and elucidate suspicious findings. OBJECTIVE: The aim of this retrospective mono-center analysis study is to evaluate the performance of CEUS in gallbladder diseases and compare it to cross-sectional imaging modalities and histopathological results as gold standard. METHODS: The retrospective study analysed 37 patients with gallbladder diseases between 2009 and 2017. All patients underwent CEUS …examinations and additional cross-sectional imaging was also performed: CT imaging on 24 (64.9% ) patients, MRI imaging on 18 (48.6% ) patients, CT and MRI imaging on (28.7% ). CEUS images were performed and interpreted by a single physician. RESULTS: CEUS imaging results of the gallbladder showed a sensitivity and specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%. CT imaging of the gallbladder showed a sensitivity of 100%, specificity of 75%, PPV of 100%, and NPV of 95%. MR imaging of the gallbladder showed a sensitivity of 100%, specificity of 93%, PPV of 75%, and NPV of 100%. CONCLUSION: Ultrasound imaging plays an essential role in the evaluation of gallbladder disease. Due to additional features of contrast-enhanced ultrasound, it is possible to differentiate gallbladder pathologic alterations by depicting its micro and macrocirculation and display important malignant features that recommends prompt management. Patients with contraindications to other cross-sectional imaging modalities benefit from this safe technique. Show more

Keywords: CEUS, gallbladder, cross-sectional imaging modalities, histopathological findings

DOI: 10.3233/CH-189404

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Ahmadizad, Sajad | Daraei, Ali | Bassami, Minoo | Rahmani, Hiwa

Article Type: Research Article

Abstract: BACKGROUND: L-Arginine, the precursor of NO might be involved in improving the cardiovascular disorders via regulation of functional properties of erythrocytes. OBJECTIVE: This study investigated the effects of L-Arginine supplementation on responses of red blood cell (RBC) properties to high intensity interval exercise (HIIE). METHODS: Ten overweight healthy men participated voluntarily in the study and performed two HIIE trials with and without L-Arginine in two separate weeks. The HIIE protocol included 12 intervals of 3-min encompassed 1-min running at 100% of vVO2 max and 2-min active recovery at 40% of vVO2 max. Three blood samples …were taken before and after supplementation, and immediately after exercise; and were used to measure red blood cell properties. RESULTS: The HIIE protocol increased hematocrit, hemoglobin and lactate significantly (P  <  0.05), but had no significant effect on RBC aggregation, RBC deformability, and fibrinogen concentration. When data were compared for two trials no significant differences between the responses of RBC properties to two HIIE protocols were detected (P  >  0.05), whereas the increases in lactate concentration following HIIE was significantly lower in L-Arginine than placebo trial (P  <  0.05). CONCLUSIONS: It is concluded that L-Arginine consumption prior to HIIE does not lead to any improvement in RBC properties during HIIE in overweight healthy men. Show more

Keywords: Intermittent exercise, nitric oxide, hemorheology, erythrocyte, blood flow

DOI: 10.3233/CH-189413

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Niessen, C. | Beyer, L.P. | Haimerl, M. | Schicho, A. | Stroszczynski, C. | Wiggermann, P. | Jung, E.M.

Article Type: Research Article

Abstract: PURPOSE: To assess the postprocedure findings after percutaneous irreversible electroporation (IRE) of hepatocellular carcinoma (HCC) in contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Percutaneous IRE was performed in a total of 22 patients with 24 HCC tumours following interdisciplinary tumour board review. The lesions were documented using CEUS before, immediately and within 24 hours after IRE. During follow-up CEUS was performed at 6 weeks and 3, 9, and 12 months after ablation. Two experienced radiologists evaluated the acquired CEUS image date in a consensus reading. RESULTS: Median tumour size before treatment was 13.7±4.8 mm (short axis) and 16.0±5.2 mm …(long axis). All HCC lesions showed arterial hyperenhancement in CEUS. Median size of the ablation defect after ablation was 29.3±5.2 mm (short axis) and 31.6±5.6 mm (long axis). After IRE all tumours showed complete devascularization. The size of the ablation defects showed significant shrinkage and reduced peripheral enhancement in the course of follow-up. At 12 months follow-up the ablation defect size decreased to 16.7±4.3 mm (short axis) and 18.3±4.1 mm (long axis). CONCLUSION: CEUS showed a complete devascularization of HCC tumours after IRE. Post-intervetional peripheral enhancement returned to normal during follow-up and may represent zones of reversible damage of cellular integrity through electroporation. A significant shrinkage of the ablation defects during 12 month of follow-up was seen in all cases. Show more

DOI: 10.3233/CH-180449

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Negrão de Figueiredo, G. | Mueller-Peltzer, K. | Zengel, P. | Armbruster, M. | Rübenthaler, J. | Clevert, D.A.

Article Type: Research Article

Abstract: BACKGROUND: Radiologic imaging, especially ultrasound has an important role in the assessment of gallbladder alteration. Contrast-enhanced ultrasound (CEUS) is an easy and fast imaging technique that overcomes the limitations of greyscale ultrasonography. It is a safe tool that can be used as an additional imaging modality in order to elucidate and differentiate gallbladder pathological findings. OBJECTIVE: The aim of this retrospective study analysis is to assess the diagnostic performance of CEUS in gallbladder alterations and compare the results to the histopathological findings. METHODS: A total of 17 patients between 2009 and 2017 with uncertain gallbladder …appearance were retrospectively analysed. A single experienced physician with more than fifteen years’ experience performed CEUS examinations by applying a second-generation blood pool agent (SonoVue ® , Bracco, Milan, Italy). Archived images were interpreted by the same physician and compared to the histopathological findings. RESULTS: CEUS results when correlated to the respectively pathologic findings presented a sensitivity of 100%, a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%. All patients were successfully examined without any adverse reaction. CONCLUSION: In conclusion, the excellent results in this study acknowledged that CEUS is a feasible alternative tool to differentiate gallbladder pathologic alterations. Show more

Keywords: CEUS, gallbladder, histopathological findings

DOI: 10.3233/CH-189405

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

Authors: Mueller-Peltzer, K. | Negrao de Figueiredo, G. | Graf, T. | Rübenthaler, J. | Clevert, D.-A.

Article Type: Research Article

Abstract: BACKGROUND: Renal cell carcinomas (RCC) represent a heterogeneous group of hypo- and hypervascularized malignancies. Using contrast-enhanced ultrasound (CEUS) specific imaging features of clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC) subtypes have been demonstrated. However, some RCCs show atypical imaging features making it difficult to distinguish between the subtypes. OBJECTIVE: This study was performed to evaluate the observed enhancement features of pRCC in CEUS and to assess the sensitivity in the diagnosis of suspected renal malignancies in a 10 year retrospective analysis at our institution. METHODS: The study population consisted of 60 …patients with histologically confirmed pRCC. All patients underwent CEUS imaging between 2005 and 2015 as part of their diagnostic workup. RESULTS: In 45 out of 60 (75%) cases the examined pRCC showed typical hypoenhancement and wash-out. 15 out of 60 (25%) pRCC showed atypical enhancement features; in 14 cases the contrast enhancement indicated a ccRCC. 1 complex cyst was falsely reported as IIF lesion. 59 out of 60 malignancies were reported as malignant using CEUS resulting in a sensitivity of 98.4%. CONCLUSIONS: CEUS is an eligible imaging technique to visualize the contrast enhancement features of pRCC. However, up to 25% of pRCCs show an atypical enhancement pattern making it difficult to distinguish it from other renal lesions. Show more

Keywords: Contrast-enhanced ultrasound, CEUS, renal cell carcinoma, RCC, enhancement features

DOI: 10.3233/CH-189406

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2018

Authors: Preuss, Stephanie | Rother, Charlotte | Renders, Lutz | Wagenpfeil, Stefan | Büttner-Herold, Maike | Slotta-Huspenina, Julia | Holtzmann, Christopher | Kuechle, Claudius | Heemann, Uwe | Stock, Konrad Friedrich

Article Type: Research Article

Abstract: Introduction: Allograft rejection (AR), chronic allograft injury (CAI) and acute tubular necrosis (ATN) can lead to renal allograft dysfunction after kidney transplantation. Interstitial fibrosis/tubular atrophy (Banff classification 2005) describes chronic allograft injury with no specific etiology, thus explaining the common final endpoint of various (immunologic and non immunologic) etiologies. The aim of this study was to evaluate correlations between the Doppler sonographic RI-values and histopathological changes of renal allografts biopsies during rejection, acute tubular necrosis and chronic allograft injury as well as the influence of donor and recipient features on the intrarenal RI-values. Methods: 102 allograft biopsies and …ultrasound reports of 69 patients with kidney transplantation performed at the hospital Klinikum rechts der Isar (Technische Universität München, Germany) between 2009 and 2013 were analyzed retrospectively (41 biopsies of living donors, 61 biopsies of deceased donors). Chronic allograft injury was described using the IFTA (interstitial fibrosis and tubular atrophy) or the ECAI score (extended chronic allograft injury score). The ECAI score was built out of the chronic histological lesions glomerulopathy, interstitial fibrosis, tubular atrophy and fibrous intimal thickening (cg + ci + ct + cv) of the BANFF scoring. Results: Intrarenal RI-values were significantly higher in patients with allograft rejection than without rejection (median 0,79 vs. 0,73; inter quartile range: 0,20 vs. 0,13; p  = 0,018). The same was found for T-and non-T cell mediated rejection (median 0,78 vs. 0,73; inter quartile range 0,20 vs. 0,13; p  = 0,039). There were no significant differences in the RI-values between the subtypes of T-cell mediated rejection (type IA-IIB). Furthermore, there were no significant differences of RI-values regarding antibody-mediated rejection (present vs. not present) or type of rejection (T-cell- vs. antibody mediated rejection). Patients with rejection and simultaneously chronic allograft injury showed significantly higher RI-values than patients with only chronic allograft injury. Analyses using the IFTA or the ECAI score showed comparable results (IFTA p  = 0,043; Score p  = 0,021). The intrarenal RI-value was neither able to detect chronic allograft injury nor to distinguish between acute tubular necrosis and rejection. The intrarenal RI-value showed a significant correlation with recipient age (p  <  0,001) but not with donor features. Conclusion: In summary, the intrarenal RI-value can indicate a rejection but gives no clear hint to acute tubular necrosis and cannot differentiate from it. Since patients with rejection can have normal RI-values, a biopsy should always be performed in case of suspected rejection. The intrarenal RI-value has no unambiguous validity to determine intrinsic values of the renal allograft, but should rather be understood and interpreted as a systemic parameter influenced by multiple factors. Show more

DOI: 10.3233/CH-189306

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Cheung, A.T.W. | Chen, P.C.Y. | Wong, K.Y. | Banerjee, A. | Tracy, B.D. | To, W.J.

Article Type: Research Article

Abstract: Orthokeratology (Ortho-K) is an over-night hard contact lens therapy, which physically reshapes the corneal curvature in order to stabilize or temporally eliminate myopia in patients. We hypothesize that the prolonged physical contact and mechanical pressure induced by the Ortho-K lenses may create lasting inadvertent effects and damages (microangiopathy), and may bring about unwanted changes in the microvasculature of the bulbar conjunctiva. Computer-assisted intravital microscopy (CAIM) was used to view, document (via videotaping) and objectively quantify (via computer-assisted image analysis) the real-time dynamic and morphometric characteristics of the conjunctival microcirculation in long-term (at least over one year) Ortho-K patients (n  = 11) …and matched non-user control subjects (n  = 8). Ortho-K patients were instructed to wear their lenses overnight following standard protocol. During the study, the conjunctival microcirculation of the left eye of all Ortho-K lens users was viewed, frequently re-focused and videotaped, without and with the lens in place, as outlined in METHODS. The matched control subjects (non-lens wearing) were videotaped and studied in like manner. The dynamic and morphometric characteristics of each user and control subject were analyzed, quantified and summated as a severity index (SI) collectively for comparison. SI of Ortho-K lens users (4.18±1.08) differed significantly from SI of control subjects (1.75±1.39, p ≤0.05). In addition, changes in the conjunctival microcirculation (e.g., flow velocity, vessel diameter, shape change, etc) were viewed and videotaped immediately after the myopic patients put on the Ortho-K lenses. Eight of the 11 Ortho-K lens users displayed significant percentage changes (p ≤0.05) in flow velocity and 10 of 11 displayed significant percentage changes (p ≤0.05) in vessel diameter, without and with the Ortho-K lenses. The results clearly indicated that significant microvascular changes via tissue remodeling occurred, and were caused directly by the physical presence of the Ortho-K lenses. Show more

DOI: 10.3233/CH-189908

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Krüger-Genge, Anne | Dietze, Stefanie | Yan, Wan | Liu, Yue | Fang, Liang | Kratz, Karl | Lendlein, Andreas | Jung, Friedrich

Article Type: Research Article

Abstract: BACKGROUND: The formation of a functionally-confluent endothelial cell (EC) monolayer affords proliferation of EC, which only happens in case of appropriate migratory activity. AIM OF THE STUDY: The migratory pathway of human umbilical endothelial cells (HUVEC) was investigated on different polymeric substrates. MATERIAL AND METHODS: Surface characterization of the polymers was performed by contact angle measurements and atomic force microscopy under wet conditions. 30,000 HUVEC per well were seeded on polytetrafluoroethylene PTFE (θ adv  = 119°±2°), on low-attachment dish LAP (θ adv  = 28°±2°) and on polystyrene based tissue culture plates (TCP, θ adv  = 22°±1°). …HUVEC tracks (trajectories) were recorded by time lapse microscopy and the euclidean distance (straight line between starting and end point), the total distance and the velocity of HUVEC not leaving the vision field migration were determined. RESULTS: On PTFE, 42 HUVEC were in the vision field directly after seeding. The mean length of single migration steps (SML) was 6.1±5.2μ m, the mean velocity (MV) 0.40±0.3μ m·min - 1 and the complete length of the trajectory (LT) was 710±440μ m. On TCP 82 HUVEC were in the vision field subsequently after seeding. The LT was 840±550μ m, the SML 6.1±5.2μ m and the MV 0.44±0.3μ m·min - 1 . The trajectories on LAP differed significantly in respect to SML (2.4±3.9μ m, p  <  0.05), the MV (0.16±0.3μ m·min - 1 , p  <  0.05) and the LT (410±300μ m, p  <  0.05), compared to PTFE and TCP. Solely on TCP a nearly confluent EC monolayer developed after three days. While on TCP diffuse signals of vinculin were found over the whole basal cell surface organizing the binding of the cells by focal adhesions, on PTFE vinculin was merely arranged at the cell rims and on the hydrophilic material (LAP) no focal adhesions were found. CONCLUSION: The study revealed that the wettability of polymers affected not only the initial adherence but also the migration of EC, which is of importance for the proliferation and ultimately the endothelialization of polymer-based biomaterials. Show more

Keywords: Endothelial cells, migration, polymer-based biomaterials, cytokine release

DOI: 10.3233/CH-189317

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-19, 2018

Authors: Motabbakani, Noura | Lehmann, Christian

Article Type: Research Article

Abstract: Arthritis often presents with serious pain of the affected joints. The pain results mainly from underlying inflammatory processes initiated by the immune response to the degenerative structural changes within the joints and is associated with microvascular vasodilation that increases articular blood flow. Laser Doppler-based methods facilitate reliable quantification of microvascular perfusion. We hypothesize that laser Doppler-based measurements of periarticular blood flux can be utilized for assessment of arthritis pain in patients.

DOI: 10.3233/CH-189408

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-4, 2018

Authors: Schlenker, B. | Apfelbeck, M. | Chaloupka, M. | Stief, C.G. | Clevert, D.-A.

Article Type: Research Article

Abstract: Introduction: We aimed to evaluate whether PIRADS 3 lesions in multiparametric MRI (mpMRI) represent a significant risk of prostate cancer (PCa) in a real-world setting of different referring radiologic institutes. Materials and methods: Between May 2015 and October 2017, a total of 408 patients were referred to our clinic for MRI-ultrasound fusion targeted biopsy of the prostate (FusPbx) due to suspected prostate cancer. In all patients, preoperatively an mpMRI of the prostate was performed by altogether 62 different radiologic institutes. Prostate lesions were classified according to the PIRADS system. A PIRADS 3 lesion was diagnosed in …41 patients. FusPbx was performed transrectally using a Philips EPIQ 7 (Philips Medical Systems, Bothell, WA) scanner with plane wise fusion of ultrasound and MRI image data. In addition to FusPbx in each patient a randomized 12-core transrectal ultrasound guided biopsy (USPbx) was performed. Results: Mean PSA Level was 9.5 ng/ml (range: 1– 26 ng/ml), mean patients age was 66.1 years (48.6– 80.4). In 11/41 patients (26.8%) prostate cancer was diagnosed by FusPbx of the PIRADS 3 lesion. In the target lesion PCa was classified as Gleason Score 3+3 in 5 patients, as 3+4 in 3, 4+3 in 1, 4+4 in 1 and 4+5 in 1 patient. In patients with negative FusPbx USPbx revealed PCa in another 7 patients (17.1%). In 5 of these GS 3+3 PCa was found, in another 2 patients GS 3+4 PCa. Conclusions: PIRADS 3 lesion indicates an equivocal likelihood of significant prostate cancer. In our series the overall PCa detection rate was 26.8% and 14.6% for clinically significant cancer in PIRADS 3 lesions. This evokes the question, if PIRADS 3 lesions could be surveilled only. The findings should be confirmed in a larger series. Show more

Keywords: Prostate cancer, multiparametric MRI, image fusion, PIRADS score, MRI-ultrasound fusion biopsy

DOI: 10.3233/CH-189407

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2018

Authors: Wang, Weiwei | Xu, Xun | Li, Zhengdong | Kratz, Karl | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: Non-swelling hydrophobic poly(n -butyl acrylate) network (cPn BA) is a candidate material for synthetic vascular grafts owing to its low toxicity and tailorable mechanical properties. Mesenchymal stem cells (MSCs) are an attractive cell type for accelerating endothelialization because of their superior anti-thrombosis and immune modulatory function. Further, they can differentiate into smooth muscle cells or endothelial-like cells and secret pro-angiogenic factors such as vascular endothelial growth factor (VEGF). MSCs are sensitive to the substrate mechanical properties, with the alteration of their major cellular behavior and functions as a response to substrate elasticity. Here, we cultured human adipose-derived mesenchymal stem cells …(hADSCs) on cPn BAs with different mechanical properties (cPn BA250, Young’s modulus (E ) = 250 kPa; cPn BA1100, E  = 1100 kPa) matching the elasticity of native arteries, and investigated their cellular response to the materials including cell attachment, proliferation, viability, apoptosis, senescence and secretion. The cPn BA allowed high cell attachment and showed negligible cytotoxicity. F-actin assembly of hADSCs decreased on cPn BA films compared to classical tissue culture plate. The difference of cPn BA elasticity did not show dramatic effects on cell attachment, morphology, cytoskeleton assembly, apoptosis and senescence. Cells on cPn BA250, with lower proliferation rate, had significantly higher VEGF secretion activity. These results demonstrated that tuning polymer elasticity to regulate human stem cells might be a potential strategy for constructing stem cell-based artificial blood vessels. Show more

Keywords: Poly(n-butyl acrylate), mechanical property, vascular graft, mesenchymal stem cells, VEGF

DOI: 10.3233/CH-189418

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2018

Authors: Piecuch, Jerzy | Mertas, Anna | Nowowiejska–Wiewiora, Alicja | Sławomir, Gregorczyn | Zenon, Czuba | Wiewiora, Maciej

Article Type: Research Article

Abstract: OBJECTIVE: The aim of this study was to investigate the relationship between red blood cell (RBC) aggregation and deformability and angiogenesis parameters in obese patients. METHODS: We studied 35 obese subjects and 20 non-obese people as a control group. Angiogenesis was detected using Bio-Plex Pro Human Angiogenesis Multiplex Assays. The RBC aggregation and deformability of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser – LORCA. RESULTS: The aggregation index and the syllectogram’s amplitude were significantly higher in the obese patients, whereas the aggregation half-time (t1/2 ) was …lower compared with the control group. The deformability of RBC expressed as EI was significantly lower in the obese group than it was in the control group. All angiogenesis parameters were higher in obese individuals than they were in the control group. Significant differences were observed in angiopoietin 2 (p  = 0.048), folistin (p  = 0.0017), G-CSF (p  = 0.042), HGF (p  = 0.016), and PECAM-1 (p  = 0.014). The VEGF tended to be higher in the obese patients than in the control group (p  = 0.09); nevertheless, the concentration of PDGF-BB was similar in both groups. EI at shear stresses of 18.49 Pa and 30.2 Pa was strongly correlated with all angiogenesis parameters. No correlations were found between the studied RBC aggregation indices and angiogenesis parameters. Multivariate analyses indicated that only HGF was an independent predictor of RBC deformability at 18.49 Pa (β –0.83, P  <  0.000005) and at 30.2 Pa (β –0.83, P  <  0.00005). CONCLUSIONS: The study found that there are relationships between enhanced RBC rigidity and angiogenesis status in obese subjects. Because this correlation between angiogenesis and RBC deformability is presented for the first time, the physiological importance of the relationship requires further research. Show more

Keywords: Angiogenesis, obesity, red blood cell, deformability

DOI: 10.3233/CH-180420

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

Authors: Astapenko, David | Pouska, Jiri | Benes, Jan | Skulec, Roman | Lehmann, Christian | Vink, Hans | Cerny, Vladimir

Article Type: Research Article

Abstract: BACKGROUND: Damage of the endothelial glycocalyx (EG) has been described during surgery, but the effect of different anesthesia techniques remains unknown. Perfused boundary region (PBR) evaluated by side-stream dark field (SDF) imaging of the sublingual microcirculation enables in vivo EG assessment. PBR values are inversely related to the EG thickness. OBJECTIVE: The aim of the observational study was to evaluate the changes of PBR in patients undergoing elective joint surgery under general (GA) vs. neuraxial anesthesia (NA). Our hypothesis was that PBR will be lower in patients in NA. METHODS: Sixty consecutive patients (ASA 1–3) …undergoing elective total knee or hip replacement under GA or NA were included in this prospective observational cohort study. PBR in the sublingual microcirculation was recorded in each patient using SDF at two time points - before surgery and 2 hours after surgery. RESULTS: Before surgery, there was no significant difference in baseline PBR between groups (NA: 1.95μ m (±0.24); GA: 2.02μ m (±0.26; p  = 0.098). Postoperatively (2 hours after surgery) PBR was significantly increased in both groups with respect to baseline values (NA: 2.09μ m (±0.19), GA: 2.20μ m (±0.25); p  <  0.001). In the GA group, postoperative PBR values were significantly higher than in the NA group (p  = 0.006). CONCLUSION: Joint surgery led to significant increases of PBR. Patients in the GA group had significantly higher PBR values 2 hours after surgery compared to NA group. This might implicate that NA is associated with less EG damage then GA in elective hip/knee surgery. Show more

Keywords: Endothelial glycocalyx, neuraxial anesthesia, joint surgery

DOI: 10.3233/CH-180428

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Zhan, Jia | Diao, Xuehong | Chen, Yue | Wang, Wenping | Ding, Hong

Article Type: Research Article

Abstract: The objective of this research was to investigate the clinical value of contrast-enhanced ultrasound (CEUS) for prediction of cervical lymph node metastasis (CLNM) in papillary thyroid cancer (PTC). One hundred and eighty-six patients with PTC confirmed by fine needle aspiration (FNA) were preoperatively performed CEUS.A multivariate analysis was performed to predict CLNM by 15 independent variables. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance. There were totally 37 patients with CLNM confirmed by pathology. Multivariate analysis demonstrated that intensity at peak time, capsule contact and size on CEUS were the three strongest …independent predictors for CLNM. ROC analyses of these characteristics showed the areas under the curve (Az), sensitivity, and specificity were 0.650, 48.6 %, 79.8 %; 0.586, 67.6%, 49.7%; and 0.612, 56.8%, 64.4% for intensity at peak time, capsule contact, and size, respectively. The CEUS patterns of PTC are relative to not only the size of PTC but also the possibility of CLNM after thyroidectomy. CEUS seem to be a tool to predict CLNM in PTC patients. Show more

Keywords: Contrast-enhanced ultrasound (CEUS), papillary thyroid carcinoma (PTC), cervical, cervical lymph node metastasis (CLNM), fine needle aspiration (FNA)

DOI: 10.3233/CH-180454

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2018

Authors: Lee, Sang Bae | Kim, Yu-Sik | Kim, Jung Hye | Park, Kahui | Nam, Ji Sun | Kang, Shinae | Park, Jong Suk | Shin, Sehyun | Ahn, Chul Woo

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Hemorheologic alterations have been suggested to play a role in the pathogenesis of diabetic microvascular complications. We measured various hemorheologic parameters and assessed their possible role as a diagnostic tool for diabetic nephropathy (DN). METHODS: 248 subjects with type 2 diabetes and 222 subjects with prediabetes were included in this study. Hemorheologic parameters, including erythrocyte sedimentation rate (ESR), elongation index at 3 Pa (EI) were measured using microfluidic hemorheometer. Various metabolic parameters were measured from fasting blood samples. The subjects were stratified into three groups according to classification of DN by urinary albumin to creatinine …ratio (ACR) and four groups by estimated glomerular filtration rate (GFR), than analyzed. RESULTS: Significant differences were observed in metabolic and hemorheologic parameters according to progression of DN. Among them, (Fibrinogen×ESR)/ EI differed in all three groups of urinary ACR. In multiple regression analysis, (Fibrinogen×ESR)/ EI was an independent predictor of urine ACR after adjusted with confounding factors (ß  = 0.010, p  <  0.001). (Fibrinogen×ESR)/ EI also showed significant difference no or minimal CKD stage, moderate CKD and severe CKD classified by GFR. This parameter showed area under curve (AUC) of the receiver operating characteristic (ROC) curve of 0.762, and moderate sensitivity and specificity to predict prevalence of microalbuminuria. CONCLUSIONS: (Fibrinogen×ESR)/ EI is a sensitive parameter for screening diabetic nephropathy. Show more

Keywords: Diabetic nephropathy, RBC deformability, hemorheology, elongation index

DOI: 10.3233/CH-180434

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Leitão Guerra, Ricardo Luz | Bastos, Mateus Abdalla | Salles, Cristina

Article Type: Letter

DOI: 10.3233/CH-180462

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 2018

Authors: Adams, Rachel A. | Potter, Stephen | Bérubé, Kelly | Higgins, Timothy | Jones, Tim | Evans, Shelley-Ann

Article Type: Research Article

Abstract: BACKGROUND: Exposure to air pollution is associated with cardiovascular disease, including increased morbidity and mortality rates. OBJECTIVE: The aim of this investigation was to assess the effect, in rats, of intratracheal instillation of particulate air pollution on biomarkers of leucocyte activation and vascular endothelial damage. METHODS: Air pollution particles (PM10) were instilled into rats, and blood samples were taken three days and six weeks post instillation. Plasma neutrophil elastase and VonWillebrand factor were measured by ELISA. RESULTS: Plasma neutrophil elastase increased from 175±44 ng/ml at baseline to 288±26 ng/ml 3 days post instillation (p … = 0.038). vWF increased from 0.160±0.015 IU/ml at baseline to 0.224±0.015 IU/ml at 3 days post and 0.208±0.01 IU/ml at 6 weeks post (p  = 0.006, ANOVA). sICAM-1 increased from 17.75±0.70 ng/ml at baseline to 19.03±0.33 ng/ml at 3 days post and 21.72±1.16 ng/ml at 6 weeks post (p  = 0.009, ANOVA). CONCLUSION: Instillation caused prolonged systemic inflammation, activation of blood leucocytes and damage to the vascular endothelium. Show more

Keywords: Particles, cardiovascular disease, inflammation, endothelial damage and leucocyte

DOI: 10.3233/CH-180377

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Astapenko, David | Dostalova, Vlasta | Dostalova jr, Vlasta | Kraus, Jaroslav | Radochova, Vera | Dostal, Pavel | Ticha, Alena | Hyspler, Radomir | Lehmann, Christian | Cerny, Vladimir

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: The endothelial glycocalyx (EG) is fragile and sensitive to damage such as exposure to hypernatremia. Our aim was to describe the influence of hypernatremia on the EG in sublingual and brain microcirculation in rabbits. METHODS: Hypernatremia was induced by intravenous administration of 10% NaCl solution. The sublingual and brain microcirculation were evaluated by the Side-stream Dark Field imaging before (T1) and 20 minutes after infusion of 10% saline (T2). Damage to the EG was quantified by automated analysis of Perfused Boundary Region (PBR) indicating the amount of penetration of red blood cells into the EG. …Syndecan-1 levels were also measured. RESULTS: Hypernatremia was reached in all 20 animals, the PBR values of the sublingual area raised from 1,98 (0,3) to 2,17 (0,18) μ m (p  = 0,05). The levels of syndecan-1 (1,23 (0,36); 1,31 (0,33) ng/l, p  = 0,3) did not mirror PBR changes. CONCLUSIONS: Hypernatremia increased the PBR within the sublingual microcirculation in our animal model, probably due to compression of the EG related to temporary intravascular hypervolemia and changes of the EG charge in RBC instead of direct damaging effect on EG, which has been excluded by rather unchanged levels of syndecan-1. Show more

Keywords: Hypernatremia, endothelial glycocalyx, sublingual microcirculation, syndecan

DOI: 10.3233/CH-189907

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Kauffmann, Philipp | Troeltzsch, Markus | Brockmeyer, Phillipp | Bohnenberger, Hanibal | Manzke, Marietta | Martin, Canis | Gaayathiri, Suntharalingam | Schliephake, Henning | Prantl, Lukas | Aung, Thiha

Article Type: Research Article

Abstract: INTRODUCTION: The oral squamous cell carcinoma (OSCC) is a leading cause of death in human malignancies. The aim of this study is to integrate the CAM Assay as a reliable and good working in vivo model for the evaluation of OSCC tumor samples and its growth into the clinical work flow. MATERIAL AND METHODS: Fresh human Tumor samples (OSCCs) 1×1 cm in size were cut into 350–450μ m thick slices by a Vibratome and put on the prepared CAM model. After growth of the tumor tissue on the CAM, we started with topical induction of proinflammatory cytokines (TNFα …) and growth factors (TGFβ ). After further growth of the tumor on the assay, we explanted the tumor tissue and first performed microscopic and then immunohistochemical examinations. E-cadherin and vimentin were used as Epithelial-to-mesenchymal transition (EMT) -makers and the histologic preparations were evaluated histomorphometrically. The results were correlated with clinical parameters of the patients. RESULTS: Under TNFα , the small tumors (T1 / T2) show higher E-cadherin expression than larger tumors (T3 / T4). The vimentin expression under TNFα behaved in the opposite direction, at T1 / T2 the expression decreased in T3 / T4 increased. Furthermore, an increased E-cadherin expression in N0 and diminished E-cadherin expression in N1 / N2b patients could be detected depending on the N-stage of the patients. Vimentin, on the other hand, was reduced in the N0 group and expressed more frequently in the N1 / N2b group. TGFβ induction also led to increased expression of vimentin in the T3 / T4 tumors and N1 / N2b stages. CONCLUSION: By integrating a CAM assay into the clinical workflow, tumors with preserved tumor architecture can be cultured and subjected to histological and molecular biology studies. Effects on biological behavior are recognizable and demonstrable in this model. The key markers E-cadherin and vimentin alone are not sufficient to represent the complexity of the EMT in this model. Further molecular biology and signaling pathway analyzes are necessary. Show more

DOI: 10.3233/CH-189315

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

Authors: Rieger, Juliane | Hopperdietzel, Carsten | Kaessmeyer, Sabine | Slosarek, Ilka | Diecke, Sebastian | Richardson, Ken | Plendl, Johanna

Article Type: Research Article

Abstract: BACKGROUND: Human and equine patients are known to frequently develop vascular complications, particularly thrombosis both in veins and arteries as well as in the microvasculature. OBJECTIVE: The aim of the present study was to investigate and compare the angiogenic response of human and equine endothelial cells to lesions in an in vitro scratch assay. METHODS: Endothelial cells from human umbilical vein (HUVEC), abdominal aorta (HAAEC) and dermal microvasculature (HDMEC) as well as equine carotid artery (EACEC) and jugular vein (EVJEC) were cultured and an elongated defect was created (scratch or “wound”). Cultures were monitored over …a period of 90 hours in a life cell imaging microscope. RESULTS: In the human endothelial cell cultures, there was a uniform and continuous migration of the cells from the scratch fringe into the denuded area, which was closed after 17 (HUVEC), 15 (HAAEC) and 26 (HDMEC) hours. In the equine endothelial cell cultures, a complete closure of the induced defect occurred after 17 (EVJEC) and 35 (EACEC) hours. CONCLUSIONS: In the equine arterial cells, the delay in closure of the denuded area seems to be the results of a disoriented and uncoordinated migration of endothelial tip cells resulting in slow re-endothelialization. Show more

Keywords: Equine, horse, human, endothelial cells, life cell imaging, scratch assay, wound healing, angiogenesis, cell migration, collective cell migration

DOI: 10.3233/CH-189316

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2018

Authors: Probst, Ute | Sieron, Dominik | Bruenn, Karin | Fuhrmann, Irene | Verloh, Niklas | Stroszczynski, Christian | Jung, Ernst-Michael | Wiggermann, Philipp | Haimerl, Michael

Article Type: Research Article

Abstract: PURPOSE: Contrast enhanced magnetic resonance imaging (MRI) is able to assess liver function by characteristic changes of signal intensity (SI). The aim was to evaluate dynamic contrast-enhanced SI-indices of the abdominal aorta, portal vein and liver. METHODS: 72 patients underwent Gd-EOB-DTPA-enhanced MRI and a 13 C-methacetin-based liver breath test (13 C-MBT) for evaluation of liver function. Region-of-interest measurements in the liver, abdominal aorta and portal vein during native, arterial (AP), late arterial (LAP), portal venous (PVP) and hepatobiliary phase (HBP) were applied to analyze SI-indices in T1-weighted volume-interpolated breath-hold examination (VIBE) sequences with fat-suppression and relative enhancement (RE) …analysis was performed. RESULTS: The liver (p  <  0.001), the portal vein (p  <  0.001) and abdominal aorta (p  = 0.002) showed significant decrease of REs with decreasing liver function. An increasing trend between logarithmic values of 13 C-MBT and REs of hepatic parenchyma (HBP; r  = 0.662, p  <  0.001), portal vein (PVP; r  = 0.532, p  <  0.001) and abdominal aorta (PVP; r  = 0.421, p  <  0.001) was observed. CONCLUSIONS: RE measurements of the hepatic parenchyma proofed to be a trustable evaluation method for liver function evaluation. In accordance with liver function, changes of REs in the portal vein and abdominal aorta occur. Show more

Keywords: Dynamic contrast enhanced MRI, 13C-methacetin liver function breath test, HCC, liver metastases, hepatic parenchyma, portal vein, abdominal aorta, signal intensity, relative enhancement

DOI: 10.3233/CH-189324

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Zou, Jie | Wang, Weiwei | Kratz, Karl | Xu, Xun | Nie, Yan | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: Polycarbonate (PC) substrate is well suited for culturing human mesenchymal stem cells (MSCs) with high proliferation rate, low cell apoptosis rate and negligible cytotoxic effects. However, little is known about the influence of PC on MSC activity including senescence, differentiation and secretion. In this study, the PC cell culture insert was applied for human MSC culture and was compared with polystyrene (PS) and standard tissue culture plate (TCP). The results showed that MSCs were able to adhere on PC surface, exhibiting a spindle-shaped morphology. The size and distribution of focal adhesions of MSCs were similar on PC and TCP. The …senescence level of MSCs on PC was comparable to that on TCP, but was significantly lower than that on PS. MSCs on PC were capable of self-renewal and differentiation into multiple cell lineages, including osteogenic and adipogenic lineages. MSCs cultured on PC secreted a higher level inflammatory cytokines and pro-angiogenic factors including FGF2 and VEGF. Conclusively, PC represents a promising cell culture material for human MSCs. Show more

Keywords: Polycarbonate, human mesenchymal stem cells, differentiation, cytokine secretion, senescence

DOI: 10.3233/CH-189322

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Fuhrmann, Irene | Brünn, Karin | Probst, Ute | Verloh, Niklas | Stroszczynski, Christian | Jung, Ernst Michael | Wiggermann, Philipp | Haimerl, Michael

Article Type: Research Article

Abstract: BACKGROUND: The diagnostic value of Doppler ultrasonography of the portal vein for the evaluation of liver function is still contradictory. OBJECTIVE: Aim of this study was to test the relationship between clinical liver function tests based on MRI and breath testing and blood flow in the portal vein. METHODS: The portal vein velocity was measured by color coded Doppler ultrasonography (CCDS) and tested against the relative enhancement (RE), a MRI-based index of liver function. The signal intensity in the liver parenchyma was assessed before (pre) and after (post) administration of contrast agent, the RE was calculated …afterwards. Further, the liver function was also assessed using a 13 C-Methacetin-based breath test. The blood flow in the portal vein was tested for possible correlation applying Pearson’s correlation coefficient. RESULTS: Using CCDS, all patients show a hepatopetal portal blood flow. The portal vein velocity is decreasing with progression of liver damage and there was a significant correlation of portal velocity with SI post (r = 0.411, p = 0.024). However, the portal velocity did not correlate significantly with the 13 C-MBT readout (r = 0.233; p = 0.216), SI pre (r = 0.271, p = 0.147) or the relative enhancement (r = 0.303; p = 0.103). CONCLUSIONS: The results of this proof-of-principle study indicate that CCDS-based assessment of portal velocity is of only limited value for the evaluation of liver function. Show more

Keywords: 13C-methacetin liver function breath test, contrast enhanced MRI, doppler, liver function, portal vein velocity, signal intensity, sonography

DOI: 10.3233/CH-189323

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Salha, Sonia | Gehmert, Sebastian | Brébant, Vanessa | Anker, Alexandra | Loibl, Markus | Prantl, Lukas | Gehmert, Sanga

Article Type: Research Article

Abstract: INTRODUCTION: Mesenchymal stem cells (MSCs) have been described in breast cancer models to migrate towards carcinoma and integrate into tumor associated stroma supporting tumor growth, increasing their metastatic potency and contributing to tumor-angiogenesis. Platelet-derived growth factor (PDGF) isoforms (AA, BB, CC) stimulate growth, survival and motility of MSCs and certain other cell types. Noteworthy, breast carcinomas are known to express PDGF. We aim to further shed light on i) the relevance of the different PDGF isoforms on adipose tissue derived stem cells (ASCs) migration and ii) the underlying pathway dependent on PDGF stimulation. MATERIALS AND METHODS: Breast cancer …cell lines were purchased and ASC?s were isolated from murine subcutaneous adipose tissue. The transmigration of ASC?s towards the PDGF-isoforms was assessed by using recombinant human PDGF-AA, PDGF-BB and PDGF-CC in a trans-well culture dish system. Transmigrated ASC?s were quantified in 5 randomly selected fields per condition using fluorescence microscopy after calcein-staining. PDGF-BB depended transmigration of ASC?s was verified by downregulation and overexpression of PDGF-BB in breast cancer cell line using shRNA-technique. In addition, a PI3-kinase inhibitor (LY294002) and a MAP-kinase inhibitor (PD98059) were used to identify the pathway involved in the PDGF-BB mediated migration of ASC?s towards tumor. RESULTS: ASC?s transmigration significantly increased towards PDGF AA at 50 ng and only showed further increase by 500 ng which was similar to cell behavior when exposed to PDGF CC. In comparison, PDGF-BB significantly increased ASC?s transmigration already at a low level of 5 ng with further significant increase for 20 ng and 40 ng. Cell transmigration was blocked with PDGFR-α antibodies but only for PDGF-AA and PDGF-CC whereas PDGFR-β blockage showed a significant effect on transmigration for PDGF-BB and PDGF-CC but not for PDGF-AA. Neutralizing antibodies in combination with PDGF receptor blockage confirmed findings. In addition, only PI3-kinase inhibitor but not the MEK-1 selective inhibitor caused a significant decrease of transmigration for ASCs towards breast cancer cells. DISCUSSION: The transmigration of ASC's is most significantly enhanced by PDGF-BB via the PI3-kinase pathway. This data support that PI3-kinase is an important key player for MSC migration towards malignancy which need further research to prevent tumor progression in early disease stage. Show more

Keywords: Mesenchymal stem cells, migration, breast cancer, PDGF-BB, PI3K pathway

DOI: 10.3233/CH-189319

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Kammerer, Sarah | Küpper, Jan-Heiner

Article Type: Research Article

Abstract: BACKGROUND: Drug induced liver injury (DILI) is the most frequent cause for failure of new drugs in clinical studies. Thus, toxicity studies are indispensable during drug development. The proliferative human liver cell strain HepaFH3 with promising primary-like cellular properties might be a suitable liver model for such studies, but their cytochrome-P450 (CYP) expression is still in low ranges compared to freshly isolated primary human hepatocytes. OBJECTIVE: We aimed to optimize the induction protocol for CYP1A2 and CYP3A4 in HepaFH3 to obtain a physiologically relevant in vitro liver model. METHODS: CYP1A2 and CYP3A4 …were induced by omeprazole and rifampicin, respectively. Induction of the two CYPs was measured by qRT-PCR, immunofluorescence and by P450 Glo enzyme activity assays. RESULTS: The optimized protocol made the experimental design six days shorter than the original procedure. CYP1A2 mRNA levels were induced 118-fold, CYP3A4 levels 36-fold. This result was also reflected at protein level. Enzymatic activity of CYP1A2 increased 3.7-fold and CYP3A4 activity increased 9.8-fold after induction. CONCLUSIONS: We succeeded in optimizing the induction protocol for HepaFH3 to such an extent that CYP1A2 and CYP3A4 are expressed in sufficient amounts that the cell strain can be used as a physiological relevant human liver model for in vitro toxicology studies. Show more

Keywords: Cytochrome P450, CYP induction, DILI, drug induced liver injury, HepaFH3, liver in vitro model, liver toxicity

DOI: 10.3233/CH-189321

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Zhou, Juan | Yang, Hyewon | Lehmann, Christian

Article Type: Research Article

Abstract: Sepsis is a medical condition caused by dysregulated systemic inflammatory response against infection, resulting in high mortality. Despite intensive research over the last few decades, the results from multiple clinical trials targeting specific inflammatory mediators have been disappointing. In the present study, we investigated the role of G protein-coupled receptor GPR55 modulation on immune response in an experimental sepsis model (endotoxemia). Immune response was evaluated by analyzing leukocyte-endothelial interactions and capillary perfusion in the intestinal microcirculation using intravital microscopy. In addition, the levels of plasma inflammatory cytokines were measured. The results demonstrated that GPR55 inhibition using antagonists, CID16020046 or O-1918, …significantly reduced leukocyte adherence in intestinal submucosal venules and decreased proinflammatory cytokine TNF-α and IL-6 production. These data suggest that GPR55 inhibition may be a novel therapeutic target for attenuating hyperinflammation during sepsis. Show more

DOI: 10.3233/CH-189320

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Nie, Yan | Wang, Weiwei | Xu, Xun | Zou, Jie | Bhuvanesh, Thanga | Schulz, Burkhard | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: Bioengineered cell substrates are a highly promising tool to govern the differentiation of stem cells in vitro and to modulate the cellular behavior in vivo . While this technology works fine for adult stem cells, the cultivation of human induced pluripotent stem cells (hiPSCs) is challenging as these cells typically show poor attachment on the bioengineered substrates, which among other effects causes substantial cell death. Thus, very limited types of surfaces have been demonstrated suitable for hiPSC cultures. The multilayer coating approach that renders the surface with diverse chemical compositions, architectures, and functions can be used to improve the …adhesion of hiPSCs on the bioengineered substrates. We hypothesized that a multilayer formation based on the attraction of molecules with opposite charges could functionalize the polystyrene (PS) substrates to improve the adhesion of hiPSCs. Polymeric substrates were stepwise coated, first with dopamine to form a polydopamine (PDA) layer, second with polylysine and last with Laminin-521. The multilayer formation resulted in the variation of hydrophilicity and chemical functionality of the surfaces. Hydrophilicity was detected using captive bubble method and the amount of primary and secondary amines on the surface was quantified by fluorescent staining. The PDA layer effectively immobilized the upper layers and thereby improved the attachment of hiPSCs. Cell adhesion was enhanced on the surfaces coated with multilayers, as compared to those without PDA and/or polylysine. Moreover, hiPSCs spread well over this multilayer laminin substrate. These cells maintained their proliferation capacity and differentiation potential. The multilayer coating strategy is a promising attempt for engineering polymer-based substrates for the cultivation of hiPSCs and of interest for expanding the application scope of hiPSCs. Show more

Keywords: Polymeric substrate, surface coating, induced pluripotent stem cells, cell adhesion

DOI: 10.3233/CH-189318

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Bimpong-Buta, Nana-Yaw | Jirak, Peter | Wernly, Bernhard | Lichtenauer, Michael | Knost, Thorben | Abusamrah, Thaer | Kelm, Malte | Jung, Christian

Article Type: Research Article

Abstract: BACKGROUND: Parabolic flights offer a unique platform for human experiments in short-term weightlessness. It is generally known that human organ systems react to changes of gravity. Yet, little is known about alterations of blood parameters under these conditions with special emphasis on blood rheology. OBJECTIVE: We investigated the alterations of distinct blood parameters after exposure to weightlessness. METHODS: 14 healthy volunteers underwent short-term phases of weightlessness induced by parabolic flight. At different time points (baseline, t2:1 hour after landing, and t3:24 hours after baseline), venous blood was drawn and analyzed. RESULTS: Analysis of red …blood count revealed significant decreases of hemoglobin and hematocrit post flight. While total white blood counts were unaltered, differential subset analysis revealed significant decreases of eosinophil granulocytes and monocytes. Cortisole levels were unchanged and lacked physiologic circadian decrease. Parameters of renal function were found significantly improved (GFR (ml/min/1,73m2 ): Baseline: 105 [89;109], t2:117 [98;125], t3:110 [102;119]; p = 0.0013. In the sense of mild myocytolysis, levels of myoglobin were significantly elevated post-flight with fast recovery to baseline levels. CONCLUSIONS: In the current analysis, significant alterations of blood parameters after exposure to weightlessness could be detected. These results contribute to the understanding of physiologic adaptations of the human body to weightlessness. Show more

Keywords: Blood parameter analysis, weightlessness, parabolic flight

DOI: 10.3233/CH-189314

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Vahldiek, Janis L. | Erxleben, Christoph | Bressem, Keno Kyrill | Gemeinhardt, Ole | Poch, Franz | Hiebl, Bernhard | Lehmann, Kai S. | Hamm, B. | Niehues, Stefan M.

Article Type: Research Article

Abstract: BACKGROUND: Radiofrequency ablation (RFA) is an important treatment option for hepatic tumors and metastases. Post-ablation recurrence rates are reported up to 36.5 percent and seem to depend on tumor size, intrahepatic localization of tumors and adjacent hepatic vessels. Multipolar RFA has the potential to overcome/reduce these limitations. Experimental and standardized data on achievable lesion sizes, influence of hepatic vessels and non-invasive evaluation of complete ablation is still insufficient. OBJECTIVES: The aim of this study was to evaluate the influence of intrahepatic vessels on shape and size of multipolar RF-ablation zones in healthy porcine liver and to evaluate the …appropriateness of immediate post-ablation contrast-enhanced computed tomography (CECT) in detecting RF-ablation dimensions. MATERIAL AND METHODS: We conducted multipolar RFAs in each of the livers of 10 healthy, narcotized and laparotomized domestic pigs by inserting three parallel probes with a constant probe distance and a constant energy supply. In 4 ablations we interrupted hepatic blood flow using Pringle’s maneuver. Immediate post-ablation CECT scans were acquired. After euthanasia the livers were sliced perpendicularly to the probes at the probes’ active centers. CECT scans were reconstructed equivalently in order to compare RF-lesion size and shape to the macroscopic sections. RESULTS: In total, 19 RF-lesions were analyzed. Every RF-lesion that was ablated during physiological liver perfusion showed an irregular and cloverleaf-like shape (n = 15). Interrupting the hepatic blood flow during RFA led to well-defined, round and homogeneous ablation zones which were 3.8 times larger compared to RF-lesions ablated during continuous hepatic perfusion (n = 4). We found an excellent correlation between immediate post-ablation CECT slices and macroscopic sections when comparing RF-lesion diameters and area, although CECT tended to overestimate ablation dimensions. CONCLUSIONS: The interruption of hepatic blood flow using Pringle’s maneuver during multipolar RFA with three applicators significantly reduces heat sink effects of hepatic vessels and generates large and coherent ablation zones. This approach should be considered in each case of ablation planning adjacent to larger hepatic vessels or when ablating larger tumor volumes. Immediate post-ablation CECT has limited value in detecting incomplete RFA periprocedurally. Show more

Keywords: Liver perfusion, animals, catheter ablation, electrodes, imaging, three-dimensional/*methods, multidetector computed tomography, radiography, Interventional/methods, *contrast media

DOI: 10.3233/CH-189313

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Zengel, Pamela | Notter, Florian | Clevert, Dirk A.

Article Type: Research Article

Abstract: BACKGROUND: Ultrasound is the method of choice for preoperative evaluation of masses of the parotid glands. However, existing methods do not allow for definite differentiation between the most common benign and malignant tumors. OBJECTIVE: Thus, we evaluated the benefits of Virtual Touch Quantification (VTQ) and Virtual Touch imaging quantification (VTIQ) for improving preoperative evaluation of parotid tumors. METHODS: We investigated eight lymph nodes and 41 tumors of the parotid gland via ultrasound, color Doppler ultrasound, VTIQ and VTQ shear wave imaging. Each examination consisted of pictures and videos, which were evaluated by twelve examiners. Initially, each …examiner predicted whether the mass was benign or malignant based on B-mode and Doppler images. Then each examiner viewed the VTIQ and VTQ shear wave images and reevaluated the predictions, which were then compared with the histopathological outcomes. RESULTS: In tumors, the sensitivity was 36% based only on B-mode and color Doppler sonography, which increased to 42% with the addition of VTIQ and VTQ. Likewise, the specificity also increased from 78% to 85%. CONCLUSIONS: VTQ and VTIQ provide additional data that improve the capability to distinguish between benign and malignant tumors allowing for an increase in both the sensitivity and specificity. Show more

Keywords: Parotid tumors, ultrasound, shear wave, ARFI imaging, Virtual Touch IQ, pleomorphic adenoma

DOI: 10.3233/CH-189312

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Schwarze, V. | Mueller-Peltzer, K. | Negrão de Figueiredo, G. | Lindner, F. | Rübenthaler, J. | Clevert, D.-A.

Article Type: Research Article

Abstract: BACKGROUND: Hepatic echinococcosis (HE) is a zoonosis and depicts a rare but potentially lethal disease caused by larval infestation of E. multilocularis ( alveolar echinococcosis, AE) and E. granulosus ( cystic echinocococcosis, CE). In many countries, HE is a critical public health problem. Clinically, HE patients initially are often asymptomatic for years. Depending on the echinococcal manifestations patients can later develop unspecific symptoms as fatigue, abdominal pain and may present with elevated transaminases, jaundice and hepatomegaly. The combination of grey scale ultrasound and serological tests has been the gold standard for the screening and diagnosis of HE. Besides MRI, CT …and FDG-PET scans, safe and directly accessible contrast-enhanced ultrasound (CEUS) may easily help to indirectly describe perilesional inflammation. Upon diagnosis of HE, an appropriate therapeutical strategy should be evaluated in a multidisciplinary way. OBJECTIVE: The aim of the present retrospective monocenter study is to assess the diagnostic performance of CEUS examination in the evaluation of hepatic echinococcal manifestation by comparison with CT, MRI, FDG-PET scans and histopathology. METHODS: Out of 36 patients with echinococcal disease (16 patients with E. multilocularis infection, 12 patients with E. granulosus infection and 8 patient with unspecified Echinococcus infection) 8 HE patients (4 patients with E. multilocularis , 2 patients with E. granulosus and 2 patients with unspecified echinococcal liver disease) were included in this study on whom CEUS was performed between 2008–2016. The applied contrast agent was a second-generation blood pool agent (SonoVue ® , Bracco, Milan, Italy). CEUS examinations were performed and interpreted by a single experienced radiologist with more than 15 years of experience. RESULTS: All patients were examined without occurrence of any side effects. In all 4 AE patients, contrast enhancement could be detected by means of CEUS and was confirmed by MRI or PET-CT scan. In the remaining 4 patients (CE and unspecified echinococcosis), doppler ultrasonography, CEUS and corresponding CT or MRI scans could not detect any hypervascularization of the lesions of interest. The histopathological analysis did not reveal any viable parasite material. CEUS showed a sensitivity of 100% and a specificity of 100% compared to MRI, CT or FDG-PET-CT. CONCLUSIONS: CEUS depicts a safe method for the evaluation of echinococcal liver disease. In addition to serological tests and grey scale ultrasound, CEUS imaging could be integrated as an easily accessible tool helping to describe hypervascularization as a sonomorphological correlate for active perilesional inflammation of echinococcal manifestations. CEUS may further help to differentiate between CE and AE and also to evaluate treatment outcome. Show more

Keywords: Hepatic echinococcosis, alveolar echinococcosis, cystic echinococcosis, contrast-enhanced ultrasound, CEUS

DOI: 10.3233/CH-189310

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Schlenker, B. | Apfelbeck, M. | Buchner, A. | Stief, C. | Clevert, D.-A.

Article Type: Research Article

Abstract: INTRODUCTION: Prostate cancer (PCa) is one of the most common malignancies in men. The diagnostic standard to confirm prostate cancer is the transrectal ultrasound-guided biopsy. However, this procedure is associated with the underdetection of clinically significant prostate cancer and therefore needs to be improved. In the last years MRI fusion based targeted biopsy gained importance as consequence. In this study, we evaluated the quality of MRI ultrasound image fusion and evaluated factors influencing the image fusion quality. This was done by comparing fusion quality with the histopathological findings in the defined MRI target on the one hand and the PIRADS …score on the other hand. MATERIALS AND METHODS: Single arm study including patients with elevated prostate specific antigen (PSA) and a multiparametric MRI showing a suspicious lesion underwent a MRI fusion targeted biopsy at our institution. MRI fusion targeted biopsy and an additional 12-core transrectal ultrasound (TRUS) guided biopsy was performed using the Philips Percunav device (Philips Medical Systems, Bothell, WA). The fusion accuracy was rated by two experienced clinicians (1 radiologist, 18 years of experience, 1 urologist, 5 years of experience) using a five-point rank scale (1 = best) and comparing the result with the histological findings in the target and the PIRADS score. RESULTS: The detection rate of clinically significant cancer (Gleason 7a or greater) by MRI-ultrasound fusion targeted biopsy was 58.6% (17/29) compared to 50% (19/38) in the standard transrectal ultrasound-guided approach. PCa was found in 36.4% (4/11 patients) of patients with a PIRADS 3 lesion, in 57.7% (15/26 patients) of patients with a PIRADS 4 lesion. In 76.9% (10/13 patients) of patients with a PIRADS 5 lesion PCa was diagnosed. No statistical significance was found comparing the quality of registration either with the PIRADS (p = 0.7873) nor with the Gleason score (p = 0.4376). The study is limited by the small number of patients. CONCLUSIONS: MRI fusion based targeted biopsy improves the identification of clinical significant cancer. The Gleason score of detected PCa is not influenced by the quality of fusion. Show more

Keywords: Transrectal ultrasound-guided biopsy, image fusion, prostate, prostate cancer, multiparametric MRI

DOI: 10.3233/CH-189308

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

Authors: Aung, T. | Heidekrueger, P.I. | Geis, S. | Von Kunow, F. | Taeger, C. | Strauss, C. | Wendl, C. | Brebant, V. | Prantl, L. | Hillmann, A.

Article Type: Research Article

DOI: 10.3233/CH-189309

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

Authors: Platz Batista da Silva, Natascha | Michael Jung, Ernst | Jung, Friedrich | Schlitt, Hans J. | Hornung, Matthias

Article Type: Research Article

Abstract: AIM: Aim of this study was to firstly describe reproducible, objective perfusion parameters of contrast-enhanced ultrasound (CEUS) kinetics of parathyroid gland adenoma (PA) using perfusion analysis software (VueBox® , Bracco, Italy). Thereby the efficiency of quantitative CEUS for characterization of PA should be evaluated comparing US to postoperative histopathological findings after PA resection. MATERIAL AND METHODS: 42 patients with symptoms/lab work suggestive of pHPT presented a parathyroid gland lesion in B-mode US, which was consequently analyzed by dynamic CEUS. CEUS was performed by one experienced examiner after i.v.-injection of max. 2.4 ml sulphurhexaflouride microbubbles saving digital DICOM cine …loops (up to 25 s) and images. PA were evaluated during arterial, venous and late phase (up to 3 min.) for perfusion characterization. A retrospective, blinded VueBox® perfusion analysis of arterial phase of 28/42 PA was performed by a second, independent examiner placing 3 ROIs manually in the PA (center, rim of PA, surrounding thyroid gland tissue) to objectify findings. US findings were correlated to postoperative histology after PA resection. RESULTS: Out of 42 patients with PA findings in CEUS, perfusion analysis could be performed in 28/42 cases only as some CEUS cine loops had too much moving. In three cases the second examiner could not detect PA retrospectively, in 25 cases PA were characterized correctly resulting in a sensitivity rate of 89.3 %. VueBox® perfusion analysis confirmed that PA present a persisting hypervascularization of the rim with higher TTP (mean 7.93 s centrally, 8.36 s rim-sided), mTT (mean 56.6 s centrally, 64.5 s rim-sided) and lower PE (mean 10542.93 rm2 centrally, 8909.21 rm2 rim-sided) peripherally followed by a central wash-out during later phases. RT was comparable in all defined regions. CONCLUSION: VueBox® analysis of parathyroid gland CEUS examinations seemed to be a valuable tool for quantification of a PA’s perfusion and can help to detect and localize hyperfunctional parathyroid glands prior to surgery. Show more

Keywords: Contrast-enhancend ultrasonography, 99mTechnetium-sestamibi scintigraphy, diagnostics of primary hyperparathyroidism, VueBox® , CEUS perfusion quantification, parathyroid gland adenoma

DOI: 10.3233/CH-189307

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Sardinha, Joel | MacKinnon, Sean | Lehmann, Christian

Article Type: Research Article

Abstract: RATIONALE: Alterations in human microcirculation occur in many disease states leading to morbidity and mortality, however assessing the microcirculation is not standard clinical practice. Standard microcirculation analysis using semi-automated analysis is expensive, time consuming, and expertise dependent making it unfeasible. We proposed a novel visual scoring system (microVAS) for the analysis of microcirculation videos that can be performed at the patient bedside in real time. OBJECTIVE: Validate our microVAS score by training health professionals unfamiliar with the microcirculation field to use our microVAS score and compare their scores to the standard method of semi-automated analysis using …AVA3 software. METHODS: Using a prospective double-blind study design, we recruited and trained 20 participants to use our microVAS score. Participants scored 40 videos (from 22 healthy and 18 septic patients) for MFI and PPV. The same 40 videos were analysed by an expert using the gold standard semi-automated method of analysis. The results of the participants and the expert were analysed by Pearson’s linear regression. Krippendorff’s alpha was used to assess inter-rater reliability of the participants. RESULTS: Overall correlation of MFI was r = 0.33 (95% CI 0.27–0.39), p  <  0.05; overall correlation of PPV was r = –0.11 (95% CI –0.18 to –0.04), p  <  0.05. The Krippendorff’s alpha for MFI was 0.56 (healthy videos: α = 0.34, sepsis videos: α = 0.31). For PPV Krippendorff’s alpha was 0.43 (healthy videos: α = 0.56, sepsis videos: α = 0.17). CONCLUSIONS: Overall for both MFI and PPV, there was a small correlation between our microVAS score and AVA 3 scores. Regarding inter-rater reliability both MFI and PPV showed fair agreement between raters. Going forward multiple improvements to the microVAS scoring system as well as the training program are suggested to improve reliability and consistency. Show more

DOI: 10.3233/CH-180427

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Gori, Tommaso | Anadol, Remzi

Article Type: Research Article

Abstract: Up to 50% of the patients undergoing coronary angiography present no epicardial disease. Most of these patients are women. Takotsubo cardiomyopathy, coronary microvascular dysfunction, and spontaneous coronary artery dissection are the most common syndromes that affect these patients. Their mechanisms are complex, with a interplay between neurohormonal factors and a number of other systems. The present review describes how changes in the estrogen state may lead to changes in vasomotor tone and endothelial dysfunction which result in coronary epicardial and microvascular spasm and coronary arterial wall instability in these three conditions. The sex-dependent differences in prevalence, pathogenesis, and prognosis are …described. Show more

Keywords: Tako-tsubo, microvascular disease, sex

DOI: 10.3233/CH-189302

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-5, 2018

Authors: Gerk, U. | Franke, R.P. | Krüger-Genge, A. | Jung, F.

Article Type: Research Article

Abstract: Background: Contrast-induced acute kidney injury (CI-AKI), a potentially life-threatening complication of iodinated contrast media in patients with impaired renal function, has attracted increasing attention in recent years. There is overwhelming evidence that the most important pre-disposing factor for a contrast-medium induced nephropathy is the pre-existence of a renal impairment. Methods: The registry was performed as a part of a quality management project in the Dresden-Friedrichstadt heart catheter laboratory. In compliance with the Declaration of Helsinki/Somerset West, 9,026 patients were included between 2010 and 2015. 100 patients of these were participants in a chronic dialysis program. All …patients were dialyzed on the day before angiography. In all patients a coronary angiography, in 28 patients a stent implantation and in 12 patients a surgical reconstruction had to be performed. Prior to the intervention and one, two and three days thereafter the serum creatinine was measured. Results: Up to the third day after application of the iodinated contrast medium no significant changes of the serum creatinine (baseline value: 423.3±42.6μ mol/l) occurred (ANOVA for repeated measures: p  = 0.507). On average, a slight decrease of the serum creatinine was found. All patients remained in their routine dialysis-program. 22 out of 115 patients (19.1%) died during the next three months after the procedure. Conclusion: The study revealed that the coronary angiography using Iodixanol as iodinated contrast medium did not result in an increase of serum creatinine, which was drastically elevated in these patients before application of the iodinated contrast medium. Show more

Keywords: Keywords: Iodixanol, renal insufficiency, dialysis, serum creatinine

DOI: 10.3233/CH-189304

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

Authors: Ahmed, M. | Lutze, S. | Tembulatow, M. | Daeschlein, G. | Jünger, M. | Arnold, A.

Article Type: Research Article

Abstract: Background: Chronic venous disease (CVD) is extremely common worldwide. The prevalence is increasing with age and is associated with a reduced quality of life, particularly in relation to pain, physical function and mobility. Symptomatic chronic venous insufficiency (CVI) with venous ulcer at its’ endpoint, indicates interventional surgery to cure venous reflux therewith promoting wound healing and preventing recurrence. To our knowledge up to now no coherent study has been undertaken in patients with CVI who underwent an open venous surgery concerning complications, venous hemodynamics and perioperative symptomology in one study population. This was undertaken in our retrospective, single-centre, consecutive …case-control study in a single patient population of a university clinic in northern Germany. Part I covers postoperative complications in relation with co-morbidities, co-medication and clinical presentation. Part II will focus on pre- and postoperative hemodynamics and evolution of symptoms. Methods: Records of n  = 429 (467 extremities) patients from 2009–2013 treated with open surgery were analysed. Number and type of complication were evaluated with regards to demographic parameters, co-existing medical conditions and procedure related aspects. Complications were grouped as no events (NE), neglectable adverse events (NAE), non-neglectable adverse events (NNAE) and severe (life-threatening) adverse events (SAE). Results: In 467 extremities of 429 patients with CVI 130 (27,84%) postoperative complications were observed after open surgery, thereof 64(13,7%) NAE, 66(14,14%) NNAE and 0 SAE. 29 (6,76%) patients developed a postoperative surgical site infection, thereof 4 (0,9%) with consecutive septicaemia. Except one case with nerval lesion and paraesthesia and hypoesthesia not resolving after 12 month all complications resolved within surveillance time span of 12 month. Patients developing NAE had a higher BMI (p  = 0.003), were more likely to have diabetes mellitus (p  <  0.001), and co-morbidities leading to the intake of anti-platelet or anticoagulation drugs (p  <  0.001). Metabolic syndrome (p  <  0.001) and anti-platelet or anticoagulation (p  <  0.001) could be defined as independent risk factors for the development of complications. Patients receiving open surgery of small saphenous veins had 8 times higher risk of calf muscle venous thrombosis (p  = 0.001). Conclusion: Patients with a metabolic syndrome or receiving anti-platelet therapy or anticoagulation medication should undergo open venous surgery under hospital conditions with routine postinterventional surveillance visits. Patients undergoing an open surgery of SSV are definite candidates for postoperative subcutaneous heparin thromboprophylaxis. In general Stripping below knee increases the risk of postoperative sensory deficit. This resolves in almost all patients within one year. Show more

Keywords: Keywords: Venous surgery, postoperative complication, risk factors for complications, surgical site infections, post-operative thrombosis, paraesthesia

DOI: 10.3233/CH-189305

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2018

Authors: Zhao, Huaqun | Liu, Xueling | Lei, Bei | Cheng, Ping | Li, Jian | Wu, Yedong | Ma, Zhen | Wei, Fang | Su, Hongyue

Article Type: Research Article

Abstract: BACKGROUND: The thyroid imaging reporting and data system (TI-RADS), classified and determined the risk of thyroid nodule malignancy with ultrasound scanning. Contrast-enhanced ultrasound (CEUS) is newly developed methods which could measure perfusion features. OBJECTIVE: The aim of the study was to investigate the value of diagnosing thyroid nodules using TI-RADS combined with CEUS and determine whether improvements were made to the diagnostic accuracy. METHODS: The features of conventional ultrasonography (US) and CEUS ion 117 case of thyroid nodules samples, which were confirmed by fine-needle aspiration and/or surgery, were retrospectively analyzed. The independent US and CEUS predictors …for malignancy were determined and quantified using logistic regression analysis. The receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficiency of each method in predicting malignant solid thyroid nodules. RESULTS: The TI-RADS + CEUS combination had the highest accuracy (94.02%), sensitivity (94.74%), specificity (93.33%), PPV (93.10%) and NPV (94.92%), significantly greater than that of TI-RADS alone and CEUS alone (χ 2  = 8.746, P  <  0.001; χ 2  = 9.825, P  <  0.001). The area under the ROC curve (AUC) of TI-RADS alone, CEUS alone, and combined use of TI-RADS and CEUS were 0.871, 0.884, and 0.942, respectively. The following conventional US and CEUS features based on logistic regression analysis showed significant predictive value for thyroid malignant nodules: Obscure margin, calcification, hypoechoic, low enhancement, rim-like enhancement. CONCLUSIONS: TI-RADS in combination with CEUS has superior diagnostic efficiency in the discrimination of benign and malignant thyroid lesions, compared with TI-RADS and CEUS alone. Show more

Keywords: Thyroid nodules, contrast-enhanced ultrasound, TI-RADS, Combination, fine-needle aspiration

DOI: 10.3233/CH-180457

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Xu, Hui-Xiong | Yan, Kun | Liu, Bo-Ji | Liu, Wen-Ying | Tang, Li-Na | Zhou, Qi | Wu, Jin-Yu | Xue, En-Sheng | Shen, Bin | Tang, Qing | Chen, Qin | Xue, Hong-Yuan | Li, Ying-Jia | Guo, Jun | Wang, Bin | Li, Fang | Yan, Chun-Yang | Li, Quan-Shui | Wang, Yan-Qing | Zhang, Wei | Wu, Chang-Jun | Yu, Wen-Hui | Zhou, Su-Jin

Article Type: Research Article

Abstract: Ultrasound elastography has been introduced into clinical practice for a decade and arisen continuous increasing attention worldwide. Shear wave elastography (SWE) is a further extension of ultrasound elastography on the basis of strain elastography, providing a two-dimensional distribution map of tissue stiffness and quantitative measurement of the tissue stiffness in Young’s modulus (kPa) and/or shear wave speed (m/s). The Society of Ultrasound in Medicine, Chinese Medical Association (CMA) has recently released a series of guidelines for the use of SWE, including the technique and principle of SWE, and use of SWE in liver fibrosis, breast, thyroid, and musculoskeletal system. Herein, …a part of SWE in thyroid nodules is presented. In this guideline, the background, classification and technology of SWE, examination methods, diagnostic performance, prognosis evaluation, reproducibility, and limitations are discussed and recommendations are given. The recommendations are based on the published literatures with regard to SWE with different levels of evidence, particularly a mid-term result of the prospective multi-center clinical trial of SWE in thyroid, as well as the Society of Ultrasound in Medicine, CMA expert’s consensus. The document provides an overall analysis of SWE in thyroid from clinical perspective, which aimed to provide recommendations to the clinicians with regard to the management of thyroid nodules by the assistance of SWE. Show more

Keywords: Thyroid, ultrasound, shear wave elastography, elastography, guideline

DOI: 10.3233/CH-180452

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-22, 2018

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

Article Type: Research Article

Abstract: BACKGROUND: Magnetocardiography (MCG) has been proposed as a non-invasive and functional technique with high accuracy for diagnosis of myocardial ischemia. OBJECTIVE: This study sought to develop a novel scoring system of MCG for predicting the presence of significant obstructive coronary artery disease (CAD). METHODS: In a training set of 108 subjects, predictors of ≥70% stenosis in at least one major coronary vessel were prospectively identified from MCG variables. The final model was then retrospectively validated in a separate set of 45 subjects. RESULTS: In the multivariable logistic regression, among those …in the training set, elevated scores were predictive of ≥70% stenosis in all subjects (OR: 40.85; 95% CI: 6.28–265.90; p  <  0.001). In the validation set, the score had an area under the receiver-operating characteristic curve of 0.91 (p  <  0.001) for ≥70% stenosis. At an optimal cutoff, the score had 89% sensitivity, 77% specificity, 74% positive predictive value (PPV), 91% negative predictive value (NPV), and 82% accuracy for ≥70% stenosis. Partitioning the score into three levels of predicted risk, 91% of subjects could be identified or excluding CAD (81% PPV and 84% NPV). CONCLUSION: We described an MCG score with high accuracy for predicting the presence of anatomically significant CAD. Show more

Keywords: Magnetocardiography, scoring, coronary artery disease, diagnosis

DOI: 10.3233/CH-189301

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Unver, Fatma | Kilic-Toprak, Emine | Kilic-Erkek, Ozgen | Korkmaz, Halil | Yasin, Ozdemir | Oymak, Burak | Oskay, Alten | Bor-Kucukatay, Melek

Article Type: Research Article

Abstract: BACKGROUND: The Nordic hamstring exercise (NHE) has been proven to be an effective preventive technique for hamstring injuries. Hemorheological parameters (Erythrocyte deformability and aggregation) play a critical role in exercise influencing oxygenation. Although previous studies presented hemorheological alterations induced by different types of exercise, changes in red blood cell (RBC) deformability and aggregation following NHE remain unknown. Present study was designed to explore possible alterations in hemorheological and oxidative parameters after an acute bout of NHE. METHODS: 10 healthy, male, active students (mean age 19.9±0.23, BMI: 21.56±0.54) participated to the study. They performed a single session of seven-repetitions …of NHE followed by a familiarisation period. Blood samples were obtained before and immediately after the exercise from the antecubital vein. Hemorheological parameters were measured by an ektacytometer. RESULTS: NHE didnt change deformability, hematocrit and oxidative stress but, increased RBC aggregation index (AI, p  = 0.011) and decreased RBC aggregation half time (t½, p  = 0.009). CONCLUSIONS: Our results suggest that, increased RBC aggregation following an acute bout of NHE may result in increased plasma skimming and thus ease the flow of blood. Show more

Keywords: Nordic hamstring exercise, RBC deformability, erythrocyte aggregation, oxidative stress

DOI: 10.3233/CH-180402

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Kalender, G. | Milan, Lisy | Stock, U.A. | Endisch, A. | Kornberger, A.

Article Type: Research Article

Abstract: Endovascular repair of aortic aneurysms (EVAR) has become an established treatment option currently applied in an increasing numbers of patients with aortic aneurysms. Advantages include reduced surgical trauma, procedural time, intensive care unit and hospital lengths of stay, blood loss as well as morbidity and mortality. The optimal imaging modalities in EVAR follow-up as well as the appropriate intervals between these follow-ups remain subject of controversial discussion. Objective of this study was the evaluation of the realistic radiation exposure and risk estimate postop EVAR treatment. Of the follow-ups required according to the surveillance schedule during the first year …post-EVAR, only 68.3% were actually implemented. Of those required from the second year onwards, an average of 70% was actually performed. During the observation period, each patient underwent a mean of 4.3 CTAs. The median ED calculated from all CTAs was 24. 5 mSv. The minimum and maximum cumulative EDs for the entire observation period were 55 mSv and 310 mSv, respectively. Show more

Keywords: EVAR, radiation exposure, CTA, aortic aneurysms

DOI: 10.3233/CH-170344

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Gong, Nian-Mei

Article Type: Research Article

Abstract: PURPOSE: To retrospectively evaluate the role of intraoperative ultrasonography (IOUS) and contrast-enhanced IOUS (CE-IOUS) for the patients with hepatocellular carcinoma (HCC) undergoing hepatic resection (HR). METHODS: Twenty-one consecutive patients who had undergone HR for HCC were included in this study. The patients were subject to preoperative imaging modalities including preoperative ultrasonography (Pre-US) and preoperative contrast-enhanced ultrasonography (Pre-CEUS). All the patients then underwent intraoperative ultrasonography (IOUS) and contrast-enhanced intraoperative ultrasonography (CE-IOUS) during surgery. The visualization of primary HCC and additional lesions of all patients were analysed. RESULTS: Twenty-one HCCs were detected during Pre-US and the remaining six …lesions (28.6% ) were detected during IOUS and CE-IOUS. Thus the treatment plan was changed in 28.6% patients. Twenty-one HCCs (diameter, 0.6–3.0 cm; mean+SD, 1.98+0.85 cm) were measured on Pre-US and remeasured on IOUS (diameter, 0.9–3.3 cm; mean+SD, 2.19+0.84 mm) (p < 0.001). The 6 additional lesions consisted of three moderately differentiated HCCs, one cholangiocarcinoma, and two high-grade dysplastic nodules (DNs). The mean maximal diameter of the 6 additional lesions was 8.3 mm (range: 6–11 mm). The malignancy associated features such as capsule interruption, echo heterogeneity, hypo-echoic rim, and nodule in nodule pattern were more often depicted on IOUS than on Pre-US (all p < 0.01). CONCLUSIONS: IOUS detects more lesions and the treatment plan is changed in 28.6% patients. HCCs are larger on IOUS than on Pre-US. The typical imaging features of HCCs are better depicted on IOUS in comparison with Pre-US. Show more

Keywords: Hepatocellular carcinoma, intraoperative ultrasonography, contrast-enhanced intraoperative ultrasound, hepatic resection

DOI: 10.3233/CH-180431

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2018

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. Pre-press, no. Pre-press, pp. 1-1, 2018

Authors: Lachmann, Vera | Heimann, Marc | Jung, Christian | Zeus, Tobias | Verde, Pablo Emilio | Kelm, Malte | Bönner, Florian

Article Type: Research Article

Abstract: AIM The study aims to test whether simultaneous measurement of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) is feasible, safe and effective during regadenoson-induced hyperemia. METHODS AND RESULTS FFR, CFR and IMR were measured simultaneously during regadenoson (Rapiscan 400μ g) -induced hyperemia in 50 patients with stable coronary artery disease with a SYNTAX score of <22. Simultaneous measurement of FFR, CFR and IMR was technically feasible in all cases (50/50). No side effects occurred and even patients fulfilling classical contraindications for the use of adenosine (10/50) could be included. Regadenoson-induced hyperemia remained …stable after maximal pressure drop for more than 35 sec as measured by systemic aortic and distal coronary pressure. There was a significant drop in transit mean time from baseline to hyperemia of more than 50% (1.0 ± 0.6 s vs. 0.4 ± 0.2 s, p  <  0.01). Patients‘ mean IMR value was 23.4, and IMR values above 75th percentile significantly correlated with metformin demanding diabetes mellitus with OR 21.76 and nicotine abuse with OR 10.28. CONCLUSION A single intravenous regadenoson bolus via peripheral line increases coronary blood flow without harmful systemic side effects enabling interventionists to simultaneously assess FFR, CFR and IMR in patients with stable coronary artery disease. Show more

Keywords: Coronary artery disease, regadenoson, coronary hyperemia, coronary blood flow

DOI: 10.3233/CH-180386

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Mushtaq, Mazhar | Abdul Mateen, Muhammad | Kim, Uh-Hyun

Article Type: Research Article

Abstract: BACKGROUND: The viscosity of a fluid is a measure of its resistance. It is the thickness and stickiness of blood, and a direct measure of the resistance of blood to flow through the vessels. Various factors in the blood have direct or indirect impact on blood viscosity. These hemorheological factors play an important role in the pathogenesis of many diseases. Glucose is one such factor, which, when increased in the blood, causes resistance in the blood flow. OBJECTIVE: The present study is aimed to assess the changes in blood viscosity associated with hyperglycemia in rodents. METHODS: …Diabetic patients were grouped, depending on the duration of their diabetic status assessed by their increased HbA1c. Similarly rodents were subjected to acute or chronic hyperglycemic conditions in various experiments. In vivo , perfusion study was performed using micro probe in diabetic mice. Flow cytometry was used to assess the expression of VCAM-1 on endothelial surface. RESULTS: An approximate 40% increase in blood viscosity is observed in individual who were diabetic for the past 15 year than those who were diagnosed just one year back. Similarly such increase in blood viscosity was evident in different experiments of rodents. Our in vivo perfusion study did not showed conclusive finding however long term hyperglycemia can have tedious effect on flow rate. Vascular pathology which was evident from the data of flow cytometry, where increase in VCAM-1 expression on the endothelial surface was observed in response to glucose and in diabetic mice. CONCLUSIONS: Hyperglycemia implicates the blood viscosity which in turn can have tedious effect on metabolic syndromes thus causing the serious effect in the tissue perfusion of an organs. Show more

Keywords: Glucose, viscosity, HbA1c, metabolic syndrome, vascular pathology, diabetic, hyperglyecemia

DOI: 10.3233/CH-180426

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Kong, Wen-Tao | Tang, Min | Qiu, Yu-Dong | Shi, Jiong | Wu, Min

Article Type: Research Article

Abstract: OBJECTIVE: To compare the enhancement pattern of hepatic angiomyolipoma (HAML) on contrast enhanced ultrasound (CEUS) and magnetic resonance (MR). METHODS: The data of seven patients (females; age 28–52 years; mean, 42 years) with histologically proven HAMLs were retrospectively reviewed. All patients underwent CEUS and MR examination. The images were analyzed by two experienced doctors who blinded to the clinical and pathological information of cases. RESULTS: The mean diameter of the nodule was 5.7 cm (range: 3.2–10 cm). Histopathologic results revealed 4 nodules to be myomatous type and 3 nodules to be mixed type. All nodules showed hyperenhanced during …arterial phase on both CEUS and MRI. During portal and delayed phase, washout was more showed on MRI (5/7, 71.4% ) than on CEUS (2/7, 28.6% ). CONCLUSIONS: There is discrepancy of enhancement pattern between CEUS and MRI. The quick wash-in and sustained hyperenhancement on CEUS may be helpful for the diagnosis of HAML. Show more

Keywords: Hepatic angiomyolipoma, contrast enhanced ultrasound, magnetic resonance imaging, enhancement pattern

DOI: 10.3233/CH-170317

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Arihan, Okan | Yabanoglu, Samiye Ciftci | Ucar, Gulberk | Falkmarken, Neslihan Dikmenoglu

Article Type: Research Article

Abstract: BACKGROUND: Selective Serotonin Reuptake Inhibitors (SSRIs), antidepressants commonly used in cardiovascular diseases (CVDs), inhibit the re-uptake of serotonin not only into neurons but also into platelets. Hence they increase the level of serotonin in plasma. OBJECTIVE: This study was aimed to clarify the effects of two selected SSRIs on plasma serotonin level, hemorheological parameters (hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity) and selected oxidative stress markers (MDA, GSH, GSSG levels in plasma and erythrocytes). METHODS: Two different SSRIs (Fluvoxamine and Sertraline) were administered to male Sprague-Dawley rats in acute (5 days) or chronic fashion (21 …days) at 20 mg/kg/day dose. RESULTS: Aggregation amplitude (AMP) decreased significantly in the chronic sertraline and acute fluvoxamine groups; aggregation half time (t1/2) decreased significantly in the chronic fluvoxamine group. Biochemical parameters indicating oxidative stress significantly increased in the chronic sertraline group. CONCLUSIONS: Since SSRI’s are commonly used in patients with CVDs, complementary studies are needed to assess the impact of such changes in hemorheological parameters on the risk for CVD, and to reveal the effects of other SSRIs on hemorheological parameters. Show more

Keywords: SSRI, serotonin, erythrocyte deformability, erythrocyte aggregation, plasma viscosity, hematocrit, blood viscosity, hemorheology, MDA, GSH, GSSG, SOD, catalase, glutathion reductase, glutathione peroxidase, glutathione S-transferase, MAO

DOI: 10.3233/CH-170353

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Rothenberger, Jens

Article Type: Research Article

Abstract: BACKGROUND: Improvement of skin microcirculation would be beneficial in transplanted tissues and thus, there is a demand for effective, reliable and harmless angiogenic treatments. The aim of this study was to assess the effect of capsaicin application (CA), the remote effect of capsaicin application (REC), the impact of remote ischemic conditioning (RIC), and the impact of combined remote ischemic conditioning with capsaicin application (Comb) on human skin microcirculation. METHODS: Perfusion changes were assessed using a laser Doppler device (easyLDI, Aimago Lausanne). 30 healthy volunteers were enrolled and divided into two groups: 1) CA and REC: perfusion was assessed …on both forearms after application of capsaicin cream on one forearm with an exposure time of 40 minutes. 2) RIC and Comb: perfusion of one forearm was assessed after four cycles of 5 min blood occlusion and 5 min reperfusion using a tourniquet on the contralateral upper arm and application of capsaicin on the ipsilateral forearm. Baseline skin perfusion measurements of both forearms were carried out initially and were used as intra-individual reference. RESULTS: 1) Skin perfusion significantly increased after capsaicin application (CA = +328.3% , p > 0.05). There was no remote skin perfusion change due to capsaicin (REC). 2) RIC significantly improves skin perfusion (RIC = +20.0% , p < 0.05). The combination of RIC and CA does not improve skin perfusion compared to CA alone (Comb). CONCLUSIONS: The conditioning techniques RIC and CA showed a significant increase in human skin perfusion, CA being superior to RIC. However, the combination of CA and RIC showed no additional improvement potential as compared to CA alone. Furthermore, a remote effect of capsaicin application could not be demonstrated. These results encourage to analyze if the conditioning treatments are also beneficial for transplanted tissue survival. Show more

DOI: 10.3233/CH-180373

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

Authors: Ghanem, Souleiman | Somogyi, Viktoria | Tanczos, Bence | Szabo, Balazs | Deak, Adam | Nemeth, Norbert

Article Type: Research Article

Abstract: BACKGROUND: Arteriovenous fistula (AVF) may affect erythrocytes through many pathways (e.g., mechanical, inflammatory). However, these effects haven’t been elucidated completely yet. OBJECTIVE: To follow-up the hemorheological and the hematological changes in the presence of artificial carotid-jugular fistula in rats. METHODS: Female Wistar rats were subjected to sham-operated group (SG, n = 6) and to fistula group (FG, n = 10). Under general anesthesia, the right carotid artery and jugular vein were isolated via a neck incision, and in the FG carotid-jugular fistula was performed by microsurgical techniques Hematological variables, red blood cell (RBC) deformability …and membrane (mechanical) stability parameters were determined before operation and on the 1st and 6th postoperative weeks. Density separated samples (‘young’ and ‘old’ RBCs) were also tested. RESULTS: In FG group hematocrit, RBC and platelet counts increased gradually to reach highly significant level of increment on the 6th postoperative week. RBC deformability significantly was impaired. The membrane stability test showed lower deformability values after applying mechanical shearing. No significant differences were observed between density separated RBC subpopulations. CONCLUSIONS: The presence of arterio-venous fistula may lead to an increment of RBC mass and impairment of RBC deformability. These changes could be one of the pathways through which the fistula influences the microcirculation. Show more

Keywords: Carotid-jugular fistula, hemorheology, hematology, red blood cell deformability, mechanical stability

DOI: 10.3233/CH-180411

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Akbudak, Ismail Hakki | Kucukatay, Vural | Kilic-Erkek, Ozgen | Ozdemir, Yasin | Bor-Kucukatay, Melek

Article Type: Research Article

Abstract: BACKGROUND: Ozone is used intensively worldwide in treatment and research of various pathologies due to its healing effects. OBJECTIVE: The aim of this study is to investigate the effect of major ozone autohemotherapy on erythrocyte deformability and aggregation. METHODS: 10 and 50μ g/ml doses of ozone was applied for 20 minute to venous blood samples obtained from 10 healthy male volunteers. Erythrocyte aggregation, deformability were measured by an ektacytometer. Total oxidant status, total antioxidant status were measured via a commercial kit. The oxidative stress index was calculated. RESULTS: Ozone at 10 and 50μ g/ml …doses did not alter erythrocyte aggregation. 50μ g/ml ozone increased red blood cell (RBC) deformability measured at 0.53 Pa. Compared with the Control value, there was a significant increase in TOS, TAS for the doses of 10 and 50μ g/ml. The increase in TAS was found to be more significant at 10μ g/ml dose. The most obvious increase in OSI value was observed at 50μ g/ml. CONCLUSION: Our results demonstrate that although 10μ g/ml ozone has no effect on hemorheology, 50μ g/ml ozone concentration has positive effects on RBC deformability, thus circulation at 0.53 Pa corresponding to the shear stress encountered during venous circulation. Show more

Keywords: Ozone therapy, RBC deformability, erythrocyte aggregation, oxidative stress

DOI: 10.3233/CH-180417

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

Authors: Wärme, Anna | Hadimeri, Ursula | Hadimeri, Henrik | Nasic, Salmir | Stegmayr, Bernd

Article Type: Research Article

Abstract: BACKGROUND: A native AV-fistula (AVF) for access in hemodialysis (HD) is preferable. Stenosis, a major hurdle, is associated with older age and diabetes mellitus. PURPOSE: This case-control study aimed to clarify if any medical and/or laboratory factors, that can be altered, could be associated to AVF stenosis. METHODS: 33 patients with a patent AVF without need of intervention during a two year period (Controls) were matched by diagnosis and age with 33 patients (Cases), that had at least one radiological invasive examination/intervention due to suspected AVF malfunction (case-control mode 2:1). RESULTS: Cases had higher …weekly doses of Erythropoietin-Stimulating Agent (ESA) than Controls both before intervention (mean 8312±7119 U/w versus 4348±3790, p = 0.005) and after the intervention (7656±6795, versus 4477±3895, p = 0.018). Before intervention serum phosphate was higher in Cases while there was no significant difference in blood hemoglobin, weekly standard Kt/V, parathyroid hormone, calcium, albumin, C-reactive protein, smoking habits, BMI or other medication. CONCLUSION: Higher doses of ESA were administered in patients with AVF stenosis. Since ESA may cause local hypertrophic effects on the vascular endothelium, we should prescribe lower doses of ESA in patients at risk. Further studies should clarify such connection. Show more

Keywords: Arterio-venous fistula, hemodialysis, erythropoietin, stenosis, uremia

DOI: 10.3233/CH-180381

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-5, 2018

Authors: Yu, Sebastian | Hu, Stephen Chu-Sung | Yu, Hsin-Su | Chin, Yi-Ying | Cheng, Yang-Chun | Lee, Chih-Hung

Article Type: Research Article

Abstract: Background: Skin physiology measurement is receiving more attention for detecting vasculopathy in systemic sclerosis (SSc). Laser Doppler flowmetry (LDF) is a widely used physiological measurement to assess cutaneous microcirculation. However, findings of LDF may be normal during early stage of microangiopathy in SSc. Objective: We hypothesized that cold stress test combined with LDF could detect early-stage microangiopathy in patients with SSc. Methods: A 67-year-old male came with multiple ulcerations on his fingers for one year. After excluding diseases such as diabetes mellitus-related peripheral arterial occlusive disease and smoking-related Buerger’s disease, the diagnosis of SSc was made …according to the 2013 ACR/EULAR criteria. We performed LDF and angiography for a patient with SSc and compared the results. Results: Although occlusions of right ulnar and digital arteries were obvious in angiography, the baseline skin temperature and perfusion unit on right fingers remained within normal limits. While the microcirculatory abnormalities measured by LDF alone are subtle, LDF combined with cold stress test detected a significant slow recovery of skin blood flow 40 minutes after cold immersion. Conclusions: In conclusion, there may be discordance between macrovasculopathy and baseline microcirculatory blood flow in SSc. In such a case, cold immersion test is essential to measure the dynamic change and slow recovery of blood flow. Show more

Keywords: Angiography, capillaroscopy, laser Doppler flowmetry, systemic sclerosis, vasculopathy

DOI: 10.3233/CH-180419

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2018

Authors: Wiewiora, Maciej | Mertas, Anna | Nowowiejska–Wiewiora, Alicja | Kozlowski, Andrzej | Czuba, Zenon | Piecuch, Jerzy

Article Type: Research Article

Abstract: BACKGROUND: It is known that obesity is associated with alterations in blood rheology and venous hemodynamics. Another recent study has confirmed that adipose tissue is actively involved in angiogenesis through secretion of biologically active substances. OBJECTIVE: The aim of this study was to investigate the impact on the venous haemodynamics of the femoral vein on angiogenesis status in morbidly obese patients. METHODS: We studied venous haemodynamics and angiogenesis in a prospective study of obese and non-obese individuals. The venous wall shear stress (WSS) was calculated from the blood viscosity and the shear rate was calculated assuming …Newton’s law. Angiogenesis was detected using Bio-Plex Pro Human Angiogenesis Multiplex Assays (Bio-Plex 200 Systems). RESULTS: The shear rate (P < 0.000005) and the wall shear stress (P < 0.01) were significantly lower in the obese patients compared with the control subjects. All angiogenesis biomarkers were significantly higher in obese patients compared to the control group. Multivariate analyses identified waist circumference as an independent predictor for PECAM-1 (β = – 0.69, P < 0.0001) and for VEGF (β = – 0.60, P < 0.001); analyses identified WSS as an independent predictor for follistatin (β = – 0.59, P < 0.001), for PECAM-1 (β = – 036, P < 0.05) and for VEGF (β = – 0.42, P < 0.05). For angiopoietin 2 (β = – 0.35, P = 0.064) and HGF (β = – 0.31, P = 0.074), WSS tended to be a significant predictor. CONCLUSIONS: The results indicated that obesity-associated decreases in shear stress of the venous system lead to upregulation of angiogenesis, expressed by increased levels of endogenous positive regulators of angiogenesis. Show more

Keywords: Obesity, angiogenesis, vascular disease

DOI: 10.3233/CH-180414

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Beral, Laurence | Lemonne, Nathalie | Romana, Marc | Charlot, Keyne | Billaud, Marie | Acomat, Malik | Zorobabel, Coralie | Nader, Elie | Etienne-Julan, Maryse | David, Thierry | Connes, Philippe

Article Type: Research Article

Abstract: OBJECTIVE: Our study investigated the prevalence of retinopathy and maculopathy in sickle cell patients and tested the association between these two conditions. In addition, we tested whether hematological and hemorheological parameters, as well as genotype, were involved in the development of these two conditions. METHODS: Seventy sickle cell adult patients were recruited: 37 with sickle cell anemia (SCA) and 33 with sickle cell hemoglobin C disease (SCC). All patients underwent retinal examination and macular ocular coherence tomography. Blood was sampled for the measurements of hematological and hemorheological parameters. RESULTS: Twenty-six patients had maculopathy and 30 had …retinopathy with no significant difference between SCA and SCC patients. No association between the presence of retinopathy and maculopathy was detected. RBC aggregation was higher and RBC deformability lower at 3 Pa in SCA patients. Blood viscosity and hematocrit were higher in SCC than in SCA patients. However, no association was found between biological parameters and the sickle ocular complications studied. CONCLUSIONS: Our study showed that retinopathy and maculopathy are common in sickle cell disease. Nevertheless, we found no association with hematological parameters, blood rheology or genotype. Show more

Keywords: Hematology, hemorheology, maculopathy, retinopathy, sickle cell disease

DOI: 10.3233/CH-180412

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Hamidpour, Mohsen | Bashash, Davood | Nehzati, Parisa | Abbasalizadeh, Mahnaz | nikoogoftar, Mahin | Hamidpour, Rafie

Article Type: Research Article

Abstract: INTRODUCTION: The human scavenger receptor class B type 1 (hSR-B1), which serves as a high affinity receptor for HDL, is expressed on platelet surface and mediates various anti-atherogenic functions. Based on the anti-thrombotic effects of HDL and the importance of HDL–SR-B1 in the formation of atherosclerotic plaque, the present study was aimed to investigate and compare the expression level of hSR-B1on platelets of CAD patients with that of normal controls. METHODS: The expressions of the hSR-B1 on platelets of 31 CAD patients with atherosclerotic plaque and 20 healthy controls were detected using flowcytometry and western blotting. Moreover, platelet …function in response to the agonists was examined by aggregometry, and the lipid panel tests were assayed using chemistry autoanalyzer. RESULTS: Our findings showed that the expression of hSR-B1 was significantly reduced on the surface of platelets from CAD patients with atherosclerotic disease, as compared with healthy controls (6/8% vs. 13/6% ) (P < 0,001). Of particular interest, we also found that the formation of aggregates after stimulation of the platelets with ADP was higher in patients with atherosclerotic disease than the controls; indicating an inverse relationship between hSR-B1 expression and the function of human platelets. CONCLUSION: Taken together, the results of the present study raise the possibility that the measurement of hSR-B1 expression on human platelets may provide a valuable insight that reflects the status of RCT in patients with atherosclerosis. Show more

Keywords: Coronary artery disease, scavenger receptor B1, platelet

DOI: 10.3233/CH-170311

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Wildner, Dane | Schellhaas, Barbara | Strack, Daniel | Goertz, Ruediger S. | Pfeifer, Lukas | Fießler, Cornelia | Neurath, Markus F. | Strobel, Deike

Article Type: Research Article

Abstract: BACKGROUND Enhancement patterns on contrast-enhanced ultrasound (CEUS) help to distinguish different liver tumors. OBJECTIVE: Assessing the diagnostic value of dynamic contrast-enhanced ultrasound (DCEUS) for the discrimination of different malignant liver lesions. METHODS: 148 malignant focal liver lesions were assessed prospectively with DCEUS (hepatocellular carcinoma = HCC; cholangiocellular carcinoma = CCC; pancreatic adenocarcinoma = PCA; breast cancer = BC; colorectal cancer = CRC; melanoma = MM). Focal-nodular-hyperplasias (FNH) served as a reference for benign lesions. DCEUS-clips were recorded continuously over three minutes. DCEUS-values were compared between the tumor entities. For better inter-individual comparability, perfusion kinetics were analyzed …considering the perfusion characteristics of the surrounding liver parenchyma (Relative Signal Intensity = RSI: lesion-liver tissue/liver tissue) at different points in time. RESULTS: Absolute signal intensity in FNH showed a tendency towards higher values compared with malignant liver lesions [Peak Enhancement(a.u.): FNH 7111.4; HCC 549.9; CCC −6654.3; PCA −7307.9; BC −4562.4; CRC −10672.9; MM −3034.1]. Washout was significantly less in FNH versus PCA and CRC, and more pronounced and earlier in PCA and CRC versus HCC [RSI 30 seconds after PE-lesion(%): FNH +52; PCA −65; CRC −76; HCC −26]. Rise Time, Fall Time and mean-Transit-Time did not differ significantly. CONCLUSIONS: DCEUS-values reflect significant differences between malignant liver lesions, especially at peak enhancement and during the washout phases. Show more

Keywords: Liver, software-based dynamic contrast-enhanced ultrasound (DCEUS), focal liver lesion, tumor, hepatocellular carcinoma, cholangiocellular carcinoma, metastasis, perfusion kinetics

DOI: 10.3233/CH-180378

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2018

Authors: Wang, Qiao

Article Type: Research Article

Abstract: OBJECTIVES: To prospectively evaluate the diagnostic performance of three-dimensional (3D) shear wave elastography (SWE) for breast lesions with quantitative stiffness information from transverse, sagittal and coronal planes. METHODS: Conventional ultrasound (US), two-dimensional (2D)-SWE and 3D-SWE were performed for 122 consecutive patients with 122 breast lesions before biopsy or surgical excision. Maximum elasticity values of Young’s modulus (Emax ) were recorded on 2D-SWE and three planes of 3D-SWE. Area under the receiver operating characteristic curve (AUC), sensitivity and specificity of US, 2D-SWE and 3D-SWE were evaluated. Two combined sets (i.e., BI-RADS and 2D-SWE; BI-RADS and 3D-SWE) were compared in …AUC. Observer consistency was also evaluated. RESULTS: On 3D-SWE, the AUC and sensitivity of sagittal plane were significantly higher than those of transverse and coronal planes (both P < 0.05). Compared with BI-RADS alone, both combined sets had significantly (P < 0.05) higher AUCs and specificities, whereas, the two combined sets showed no significant difference in AUC (P > 0.05). However, the combined set of BI-RADS and sagittal plane of 3D-SWE had significantly higher sensitivity than the combined set of BI-RADS and 2D-SWE. CONCLUSIONS: The sagittal plane shows the best diagnostic performance among 3D-SWE. The combination of BI-RADS and 3D-SWE is a useful tool for predicting breast malignant lesions in comparison with BI-RADS alone. Show more

Keywords: Breast, ultrasound, three-dimensional, shear wave elastography, quantitative analysis

DOI: 10.3233/CH-180388

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2018

Authors: Bagno, Andrea | Martini, Romeo

Article Type: Research Article

Abstract: The words “Translational” and “Medicine” have been recently coupled to indicate a combination of disciplines, resources, expertise, and techniques aimed at enhancing prevention, diagnosis, and therapies. As stated in 2015 by the European Society for Translational Medicine, translational medicine is “an interdisciplinary branch of the biomedical field supported by three main pillars: benchside, bedside and community”. By definition, Translational Medicine is a highly interdisciplinary field, which gathers several specialties aimed at improving the global healthcare system. With regard to the assessment of the microcirculatory function, it is worthwhile to mention the growing interest from both basic research and clinical …practice. Microcirculation is where the exchange of substances between blood and tissues takes place. Thus, it plays a key role in the pathophysiology of many diseases. Nonetheless, a gap does exist between the theoretical analysis of the microcirculatory function and its clinical exploitation. This gap can be due to the weak dissemination of analytical methods and theoretical results within the clinical community, which also delays the establishment of specific operative guidelines. This paper aims at encouraging, and possibly accelerating, the translation of basic research outcomes on microcirculatory function assessment into clinical applications. Show more

Keywords: Microcirculation, laser doppler fluxmetry, wavelet analysis, translational medicine

DOI: 10.3233/CH-180415

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Pu, Huan | Zhang, Xue-Li | Xiang, Li-Hua | Zhang, Jiu-Long | Xu, Guang | Liu, Hui | Tang, Guang-Yu | Zhao, Bing-Hui | Wu, Rong

Article Type: Research Article

Abstract: PURPOSE: To evaluate the efficacy of added shear wave elastography (SWE) in breast screening for women with results inconsistent between mammography and conventional ultrasounds (US). MATERIALS AND METHODS: The study consisted of 282 pathologically proven breast lesions. The cancer probability from screening by mammography and conventional US were scored using Breast Imaging Reporting and Data System (BI-RADS). Elastography was used to re-evaluate inconsistent conventional US and mammography results. The diagnostic performance of conventional US, mammography, and Combined conventional clinical imaging and SWE was compared. The clinicopathological features of all breast cancer patients with inconsistent (and consistent) conventional US …and mammography findings were compared. RESULT: Finally, 147 lesions were confirmed benign and 135 were malignant. The AUC of Combined conventional clinical imaging plus elastography imaging (0.870) was significantly higher than mammography (0.735, p  < 0.001) or conventional US (0.717, p  < 0.001) alone. Among the 135 breast cancers, 79 of the conventional US and mammography findings were consistent and 56 were inconsistent. Younger age(<50y) (p  = 0.035), non-invasive (p  = 0.037), smaller size (p  = 0.002) and negative lymph node status (p  = 0.026) were significantly associated with inconsistent findings. CONCLUSION: The added SWE in breast screening when inconsistent results from mammography and conventional US occurred is necessary and effective. Show more

DOI: 10.3233/CH-180398

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Brettner, Florian | Chappell, Daniel | Nebelsiek, Tim | Hauer, Daniela | Schelling, Gustav | Becker, Bernhard F. | Rehm, Markus | Weis, Florian

Article Type: Research Article

Abstract: BACKGROUND: Patients undergoing cardiac surgery commonly develop systemic inflammation associated with tissue edema, which impairs outcome. One main pathomechanism leading to the edema is the deterioration of the endothelial glycocalyx, a key component of the vascular barrier. In animal models hydrocortisone has proved to be protective for the glycocalyx. OBJECTIVE: This trial evaluates the effect of hydrocortisone on glycocalyx integrity in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: In a prospective, randomized interventional pilot trial, 30 patients received either hydrocortisone (100 mg over 10 min) or placebo (saline control) before surgery. Plasma concentrations of glycocalyx constituents (syndecan-1, …heparan sulfate) and various clinical parameters (respiratory and renal function, inflammatory markers, use of vasopressors, length of stay at the intensive care unit) were measured. Primary endpoint was a significant difference of glycocalyx constituents in plasma. Comparisons were made with Friedman’s and Wilcoxon tests (paired data), or the Kruskal-Wallis and Mann-Whitney U tests (unpaired data). Holm-Bonferroni method was used for post-hoc corrections. RESULTS: Heparan sulfate and syndecan-1 increased significantly during and after cardiac surgery with cardiopulmonary bypass in both groups. Whereas the maximum increase of heparan sulfate was 12.3-fold in the control vs. 3.8-fold in the pretreated group (p  < 0.05), syndecan-1 values showed no significant difference between the groups (maximal increase 3-fold). The inflammatory markers C-reactive protein and interleukin-6 were also higher in the control than in the hydrocortisone group, but there was no difference in patient mortality (zero), or in any clinical parameters. CONCLUSIONS: Pretreatment with hydrocortisone ameliorated shedding of heparan sulfate, a major constituent of the endothelial glycocalyx, in patients undergoing cardiac surgery with cardiopulmonary bypass, but had no relevant influence on various clinical parameters or patient mortality. The relatively small number of patients in this pilot study probably precluded detection of positive outcome differences. Show more

Keywords: Cardiopulmonary bypass, endothelial glycocalyx, protection, vascular barrier, hydrocortisone

DOI: 10.3233/CH-180384

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Naumann, David N. | Hazeldine, Jon | Bishop, Jon | Midwinter, Mark J. | Harrison, Paul | Nash, Gerard | Hutchings, Sam D.

Article Type: Research Article

Abstract: BACKGROUND: Preclinical studies report that higher plasma viscosity improves microcirculatory flow after haemorrhagic shock and resuscitation, but no clinical study has tested this hypothesis. OBJECTIVE: We investigated the relationship between plasma viscosity and sublingual microcirculatory flow in patients during resuscitation for traumatic haemorrhagic shock (THS). METHODS: Sublingual video-microscopy was performed for 20 trauma patients with THS as soon as feasible in hospital, and then at 24 h and 48 h. Values were obtained for total vessel density, perfused vessel density, proportion of perfused vessels, microcirculatory flow index (MFI), microcirculatory heterogeneity index (MHI), and Point of Care Microcirculation (POEM) …scores. Plasma viscosity was measured using a Wells-Brookfield cone and plate micro-viscometer. Logistic regression analyses examined relationships between microcirculatory parameters and plasma viscosity, adjusting for covariates (systolic blood pressure, heart rate, haematocrit, rate and volume of fluids, and rate of noradrenaline). RESULTS: Higher plasma viscosity was not associated with improved microcirculatory parameters. Instead, there were weakly significant associations between higher plasma viscosity and lower (poorer) MFI (p  = 0.040), higher (worse) MHI (p  = 0.033), and lower (worse) POEM scores (p  = 0.039). CONCLUSIONS: The current study did not confirm the hypothesis that higher plasma viscosity improves microcirculatory flow dynamics in patients with THS. Further clinical investigations are warranted to determine whether viscosity is a physical parameter of importance during resuscitation of these patients. Show more

Keywords: Viscosity, microcirculation, haemorrhage, trauma, fluids

DOI: 10.3233/CH-180397

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

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

Authors: Sun, Xing-Zhen | Li, Shu-Yan | Tian, Xiang-Yang | Hong, Ze | Li, Jia-Xin

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH). METHODS: Twenty-four male SD rats were randomly divided into three groups: control group, model group (HPH group) and HPH+fasudil group. The rat HPH model was established by intermittent hypoxia (IH) at atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural changes were observed in all groups. RESULTS: MPAP, RVHI and ET-1 levels were significantly higher in …HPH group than in control group, while NO was significantly lower than in control group. In addition, mPAP, RVHI and ET-1 were significantly lower in the HPH+fasudil group than in the HPH group. In the HPH group, ET-1 level was significantly and positively correlated with mPAP and RVHI, NO was negatively correlated with mPAP and RVHI levels, and ET-1 level was significantly and negatively correlated with NO level. In the HPH group, pulmonary arteriolar walls were generally thickened, and lumen stenosis was obvious; while after fasudil treatment, pulmonary arteriolar wall thickening and stenosis degree were significantly reduced. CONCLUSION: Fasudil can significantly reduce ET-l level and increase NO level in HPH rats, suppressing the development of pulmonary arterial hypertension. Show more

Keywords: Hypoxic pulmonary hypertension, fasudil, endothelin-1, nitric oxide

DOI: 10.3233/CH-160232

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2017

Authors: Zhu, Yi-Cheng | Zhang, Yuan | Deng, Shu-Hao | Jiang, Quan | Shi, Xiu-Rong | Feng, Ling-Ling

Article Type: Research Article

Abstract: BACKGROUND: Plasma cell mastitis (PCM), a common type of mastitis often mimics malignancy clinically and radiologically. OBJECTIVE: The study was designed to explore the diagnostic value of superb microvascular imaging (SMI) in differentiating PCM from malignant breast lesions. METHODS: A total of 95 breast lesions underwent conventional ultrasound (US) and SMI examination between May 2016 and April 2018. Vessels were detected in SMI in a quantitative manner. Blood flow parameters including systolic peak velocity (SPV), resistance index (RI), and pulsatility index (PI) were evaluated. We further assessed the diagnostic performances of US and US+SMI. …RESULTS: The majority of PCM were in regular shape and displayed no calcification compared with malignant breast lesions. Regarding blood flow parameters, PCM obtained significantly lower mean value of RI and PI compared with malignant lesions (P  <  0.05). The sensitivity, specificity and accuracy rate of US+SMI (84.62%, 76.47%, 83.16%) was significantly higher than those of US (78.21%, 64.71%, 75.59%). CONCLUSIONS: The present study supports that SMI is a novel ultrasound technology in revealing micro-vessels in breast lesions. The combined modality of US+SMI presented a better diagnostic performance in making a distinction between PCM and malignant breast carcinomas. Show more

DOI: 10.3233/CH-180468

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018