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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-200970

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

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

Article Type: Research Article

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

Keywords: Adenosis of breast, breast cancer, breast ultrasonography

DOI: 10.3233/CH-200943

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

Authors: Tian, Bing | Li, Wenzheng | Wu, Zheng | Gong, Minglian | Liu, Jinghua

Article Type: Research Article

Abstract: OBJECTIVE: This study applied pressure measurement to measure the hemodynamic changes in right coronary artery (RCA) donor vessels before and after the opening of the vessel in patients with left anterior descending chronic total occlusion (LAD-CTO) interventional therapy. METHODS: A total of 45 patients with LAD-CTO were divided into two groups of percutaneous coronary intervention (PCI) to observe the hemodynamic changes (fractional flow reserve [FFR] and instantaneous wave-free ratio [iFR]) before and after opening the chronic total occlusion (CTO), in order to provide collateral circulating donor vessels to the CTO, and observe the changes in iFR and FFR. …The results of these two measures were compared to determine the significance of the donor vascular function. RESULTS: A total of 45 patients with LAD-CTO successfully underwent LAD-CTO interventional therapy, and were immediately measured for FFR and iFR of the donor vessels. The FFR changes before right coronary artery flow reserve (RCAFR) was 0.73±0.083, and after the operation, this was 0.77±0.073. The iFR changes before RCAFR was 0.90±0.048, and after the operation, this was 0.93±0.034. Before and after the opening of the RCA, the FFR change (Δ FFR) and iFR change (Δ iFR) were also correlated with r  = 0.033 (0.041–0.568: P  <  0.05). A total of 19 cases had a FFR value of <0.75 before the operation, and the average FFR before and after the PCI was 0.65±0.048 and 0.72±0.057, respectively. Furthermore, the Δ FFR was 0.076±0.057 (n  = 19), and FFR was >0.75 in 26 cases. The Δ FFR was 0.017±0.0088 (n  = 26). These two groups were compared, P  = 0.0032 (P  <  0.05). CONCLUSION: The FFR and iFR results were the same in terms of RCA hemodynamic changes, after the LAD-CTO was opened. For the RCA with a preoperative FFR of <0.75, the increase in RCAFR after LAD-CTO PCI was more obvious. Show more

Keywords: Coronary artery diseas, coronary blood flow, CTO, fractional flow reserve, percutaneous coronary intervention

DOI: 10.3233/CH-200885

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

Authors: Georgieva, M. | Kammerer, S. | Prantl, L. | Jung, F. | Stroszczynski, C. | Jung, E.M.

Article Type: Research Article

Abstract: BACKGROUND: In recent years, follow-up after breast reconstruction with silicone implants and the detection of complications have been relieved by the possibility of improved diagnostic methods. METHODS: Between January 2015 and December 2019 a total of 40 patients (29–84 years) with silicone implants were included in this retrospective study. The implants were examined clinically and with modern imaging: general ultrasound imaging (US), magnetic resonance imaging (MRI), high resolution computed tomography (CT) and positron emission tomography –computed tomography (PET-CT). If necessary, a histological/cytological sample was taken. The breast implants were assessed by three radiologists specialized in breast imaging. The …grade of capsular contracture was classified according to the Baker classification. RESULTS: All 40 women obtained a clinical examination and an US diagnostic to identify early and more common complications such as implant folding and capsular fibrosis. Depending on the clinical examination and ultrasound findings additional MRI (n  = 10), CT (n  = 9) and/or PET-CT (n  = 2) were performed. 16 patients had implants folding proven with US (n  = 16), MRI (n  = 6) and CT (n  = 1). The grade of capsular fibrosis was determined according to the Baker classification. The following results were obtained in our study: 25 breast implants with Baker grade I and eleven breast implants with Baker grade II, both proven with US; one breast implants with Baker grade III and one breast implant with Baker grade IV, proven with US (n  = 2), MRI (n  = 1) and CT (n  = 1). One patient had intracapsular rupture and one patient had extracapsular rupture, both detected on CT and surgically proven. No patient had a silicone accumulation in the lymph nodes. One patient had pathologically enlarged axillary lymph nodes, which were evaluated as inflammatory changes in PET-CT. Long-term complications such as the development of malignant breast tumors could not be observed. CONCLUSION: To detect early complications after breast implant surgery, a regular clinical examination is indispensable. Imaging methods complement each other and if they are used multimodal, it is easier to identify early complications. Modern diagnostic modalities like ultrasound and magnetic resonance imaging expand the spectrum and improve diagnostic safety. Show more

Keywords: Breast implant, ultrasound, magnetic resonance imaging, capsular contracture

DOI: 10.3233/CH-209218

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

Authors: Zhang, Hong-jun | Zheng, Bo-wen | Gu, Shi-jie | Wu, Tao | Wu, Li-li | Lian, Yu-fan | Tong, Ge | Yi, Shu-hong | Ren, Jie

Article Type: Research Article

Abstract: BACKGROUND: Broad hemodynamic changes, is believed to have a profoundly damaging effect on donor livers after brain death (DBD) or cardiac death (DCD). It remains unclear whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS), the imaging modalities to evaluate perfusion, could provide more information of liver discarded. OBJECTIVE: To evaluate the ability of DUS and CEUS to predict the risk of DBD or DCD liver discarded. METHODS: The consecutive DBD or DCD donors with DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of …each donor liver were analyzed and the parameters were recorded. RESULTS: Among the 67 eligible donor livers, 15 (22.4%) were discarded and 52 (77.6%) were used. The discarded livers showed prolonged SAT of hepatic artery (0.08s vs 0.06s, OR = 2.169, P  = 0.008) on DUS, less cases with homogeneous enhancement (40.0% vs 73.1%, OR = 0.243, P  = 0.028) on CEUS, more cases with decreased enhancement (46.7% vs 15.4%, OR = 4.813, P  = 0.011), and less difference of the peak time between portal vein and liver parenchymal (0.5s vs 6.7s, OR = 4.260, P  = 0.015). The multivariable analysis showed that donor liver with prolonged SAT of hepatic artery (OR = 7.304, 95% CI: 1.195–44.655, P  = 0.031) and decreased enhancement (OR = 2.588, 95% CI: 1.234–5.426, P  = 0.012) were independent factors of liver discarded. CONCLUSIONS: DUS/CEUS could be applied as a promising predictive tool to screen high-risk liver donors. The prolonged SAT of hepatic artery on DUS and the decrease of liver donor in enhancement on CEUS, indicating hemodynamic changes in DBD and DCD donor livers, were risk factors of liver discarded. Show more

Keywords: Ultrasonography, doppler, liver transplantation, tissue and organ procurement, donor selection

DOI: 10.3233/CH-200950

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

Authors: Jung, E.M. | Wertheimer, T. | Putz, F.J. | Jung, F. | Kammerer, S. | Pregler, B. | Luerken, L. | Stroszczynski, C. | Beyer, L.

Article Type: Research Article

Abstract: AIM: To evaluate the use of dynamic contrast enhanced ultrasound (CEUS) with parametric color-coded imaging and time intensity curve analysis (TIC) for planning and follow-up after prostate arterial embolization (PAE). MATERIAL/METHOD: Before and after selective iliacal embolization by PAE with a follow up of 6 months 18 male patients (43–78 years, mean 63±3.5 years) with histopathological proven benign prostate hyperplasia were examined by one experienced examiner. A multifrequency high resolution probe (1–6 MHz) was used for transabdominal ultrasound and CEUS with bolus injections of 2.4 ml sulphur-hexafluoride microbubbles. Independent evaluation of color-coded parametric imaging before and after PAE by in …PACS stored DICOM loops from arterial phase (10–15 s) up to 1min were performed. Criteria for successful treatment were reduction of early arterial enhancement by changes of time to peak (TTP) and area under the curve (AUC) by measurements in 8 regions of interest (ROI) of 5 mm in diameter at the margin and in the center and changes from hyperenhancement in parametric imaging (perfusion evaluation of arterial enhancement over 15 s) from red and yellow to blue and green by partial infarctions. Reference imaging method was the contrast high resolution 3 tesla magnetic resonance tomography (MRI) using 3D vibe sequences before and after PAE and for the follow up after 3 and 6 months. RESULTS: PAE was technically and clinically successful in all 18 patients with less clinical symptoms and reduction of the gland volume. In all cases color-coded CEUS parametric imaging was able to evaluate partial infarction after embolization with changes from red and yellow to green and blue colors in the embolization areas. Relevant changes could be evaluated for TIC-analysis of CEUS with reduced arterial enhancement in the arterial phase and prolonged enhancement of up to 1 min with significant changes (p  = 0.0024). The area under the curve (AUC) decreased from 676±255.04 rU (160 rU–1049 rU) before PAE to 370.43±255.19 rU (45 rU–858 rU) after PAE. Time to peak (TTP) did not change significantly (p  = 0.6877); TTP before PAE was 25.82±9.04 s (12.3 s–42.5 s) and after PAE 24.43±9.10 s (12–39 s). Prostate volume decreased significantly (p  = 0.0045) from 86.93±34.98 ml (30–139 ml) before PAE to 50.57±26.26 ml (19–117 ml) after PAE. There were no major complications and, in most cases (14/18) a volume reduction of the benign prostate hyperplasia occurred. CONCLUSION: Performed by an experienced examiner CEUS with parametric imaging and TIC-analysis is highly useful to further establish prostatic artery embolization (PAE) as a successful minimal invasive treatment of benign prostatic hyperplasia. Show more

Keywords: Contrast enhanced ultrasound (CEUS), parametric imaging, time intensity curve analysis (TIC), prostate arterial embolization (PAE)

DOI: 10.3233/CH-209202

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

Authors: Kanda, Hideaki | Yamakuchi, Munekazu | Mastumoto, Kazuhisa | Mukaihara, Kosuke | Shigehisa, Yoshiya | Tachioka, Shuji | Okawa, Masashi | Takenouchi, Kazunori | Oyama, Yoko | Hashiguchi, Teruto | Imoto, Yutaka

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Turbulent blood flow in patients with aortic valve stenosis (AS) results in morphological and functional changes in platelets and coagulation factors. The aim of this study is to determine how shear stress affects platelets and coagulation factors. METHODS: We retrospectively evaluated data from 78 patients who underwent AVR to treat AS between March 2008 and July 2017 at Kagoshima University Hospital. RESULTS: Platelet (PLT) count obviously decreased at three days after AVR, and increased above preoperative levels at the time of discharge. In contrast, platelet distribution width (PDW), mean platelet volume (MPV), and …platelet large cell ratio (P-LCR) increased three days after AVR, then decreased to below preoperative levels. No differences were evident between groups with higher (HPPG >  100 mmHg) and lower (LPPG <  100 mmHg) peak pressure gradients (PPG) before AVR, whereas PLT count, PDW, MPV and P-LCR improved more in the HPPG group. Plateletcrit (PCT), which represents the total volume of platelets, increased after AVR due to decreased shear stress. High increasing rate of PCT was associated with lower PLT count, higher PDW and lower fibrinogen. CONCLUSION: Shear stress affects PLT count, PDW, and fibrinogen in patients with AS. Show more

Keywords: Aortic valve stenosis, platelet, plateletcrit, shear stress, pressure gradient

DOI: 10.3233/CH-200928

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

Authors: Mrowietz, C. | Sievers, H. | Pindur, G. | Hiebl, B. | Jung, F.

Article Type: Research Article

Abstract: In patients with peripheral arterial occlusive disease (PAOD) a restricted circulation in cutaneous microvessels has been reported. In this study the velocity of erythrocytes (very) in finger nailfold capillaries - a vascular area without upstream macroangiopathy - and also in toe nailfold capillaries - a post-stenotic area –was investigated using capillary microscopy in apparently healthy subjects and patients with PAOD. Already in finger nailfold capillaries very of patients with PAOD under resting conditions was significantly lower than in capillaries of healthy subjects. This was also true for the circulation in toe capillaries. In addition, the erythrocyte velocities under resting conditions …in the toe capillaries were significantly lower than in the finger capillaries. Similar results were found for the duration and the maximum velocity of postocclusive hyperemia. It is concluded that the resting blood flow in the skin microcirculation is impaired in PAOD patients, both under resting conditions and during postocclusive hyperemia in finger as well in toe nailfold capillaries. Show more

Keywords: Microcirculation, peripheral arterial occlusive disease, capillary microscopy

DOI: 10.3233/CH-209220

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

Authors: Teusch, V.I. | Wohlgemuth, W.A. | Uller, W. | Piehler, A.P. | Goessmann, H. | Stroszczynski, C. | Jung, E.M.

Article Type: Research Article

Abstract: INTRODUCTION: Percutaneous sclerotherapy is a well-established treatment option for venous malformations (VM). A recently established sclerosing agent is ethanol-gel. Aim of this study was to identify, if contrast-enhanced ultrasound (CEUS) with an integrated perfusion analysis allows for differentiation between untreated VM, healthy tissue, and with gelified ethanol treated malformation tissue. MATERIAL AND METHODS: In this institutional review board approved prospective study symptomatic VM patients underwent CEUS at exactly the same position before and after sclerotherapy with ethanol-gel. Two experienced sonographers performed all examinations after the bolus injection of microbubbles using a multi-frequency probe with 6 –9 MHz of …a high-end ultrasound machine. An integrated perfusion analysis was applied in the center of the VM and in healthy, surrounding tissue. For both regions peak enhancement (peak), time to peak (TTP), area under the curve (AUC), and mean transit time (MTT) were evaluated. Wilcoxon signed rank test was executed; p -values <0.05 were regarded statistically significant. RESULTS: In 23 patients including children (mean age 25.3 years, 19 females) before treatment all identified parameters were significantly higher in the VM center compared to healthy tissue (peak: p  <  0.01; TTP: p  <  0.01; AUC: p  <  0.01; MTT: p  <  0.01). Comparing the VM center before and after treatment, TTP (p  <  0.02) and MTT (p  <  0.01) reduced significantly after sclerotherapy. In surrounding tissue only peak changed after treatment in comparison to pre-treatment results (p  = 0.04). Comparing data in the VM center with surrounding tissue after sclerotherapy, results still differed significantly for peak (p  <  0.01), TTP (p  <  0.01), and AUC (p  <  0.01), but assimilated for MTT (p  = 0.07). CONCLUSION: All with CEUS identified parameters seem to be excellent tools for differentiating between VM and healthy tissue. TTP and MTT could distinguish between with ethanol-gel sclerotized VM portions and untreated malformation parts and thereby might assist the monitoring of sclerotherapy with ethanol-gel. Show more

Keywords: Contrast-enhanced ultrasound, perfusion analysis, venous malformation, sclerotherapy, ethanol-gel

DOI: 10.3233/CH-209215

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

Authors: Troebs, Johannes | Asam, Claudia | Pion, Eric | Prantl, Lukas | Aung, Thiha | Haerteis, Silke

Article Type: Research Article

Abstract: BACKGROUND: The ability to evaluate tumor development within experimental oncology is of upmost importance. However, determining tumor volumes in 3D in vivo tumor models is challenging. The chick chorioallantoic membrane (CAM) model represents an optimized xenograft model that surpasses many disadvantages that are inherent to rodent models and provides the opportunity of real-time monitoring of tumor growth. OBJECTIVE: The objective of this study was to introduce a new method that enables monitoring of tumor growth within the CAM model throughout the course of the experiment. METHODS: Sarcoma cell lines and sarcoma primary tumors were grafted …onto the CAM of fertilized chicken eggs. A digital microscope (Keyence VHX-6000) was used for 3D volume monitoring before and after tumor excision and compared it to tumor weight. RESULTS: Accuracy of tumor volumes was validated through correlation with tumor weight. In and ex ovo tumor volumes correlated significantly with tumor weight values. CONCLUSIONS: The described method can be used to assess the effects of chemotherapeutic agents on the growth of tumors that have been grafted onto the CAM and further advance personalized cancer therapy. In summary, we established a promising protocol that enables in vivo real-time tracking of tumor growth in the CAM model using a digital microscope. Show more

Keywords: Chorioallantoic membrane (CAM), in vivo tumor model, tumor profiling, rhabdomyosarcoma, sarcoma, volume measurement, 3D volume

DOI: 10.3233/CH-209216

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

Authors: Nie, Yan | Xu, Xun | Wang, Weiwei | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: BACKGROUND: The formation of spheroids is tightly regulated by intrinsic cell-cell and cell-substrate interactions. OBJECTIVE: The chitosan (CS)-coating was applied to investigate the driven force directed the spheroid formation. METHODS: The effects of CS on cell functions were studied. Atomic force microscopy was employed to measure the cell- biomaterial interplay at single cell level. RESULTS: HaCaT cells shifted from their flattened sheet to a compact 3D spheroidal morphology when increasing CS coating concentration. The proliferative capacity of HaCaT was preserved in the spheroid. The expression and activation of integrin β 1 (ITGB1) were enhanced …on CS modified surfaces, while the active to total ratio of ITGB1 was decreased. The adhesive force of a single HaCaT cell to the tissue culture plate (TCP) was 4.84±0.72 nN. It decreased on CS-coated surfaces as CS concentration increased, from 2.16±0.26 nN to 0.96±0.17 nN. The adhesive force between the single HaCaT cell to its neighbor cell increased as CS concentration increased, from 1.15±0.09 nN to 2.60±0.51 nN. CONCLUSIONS: Conclusively, the decreased cell- substrate adhesion was the main driven force in the spheroid formation. This finding might serve as a design criterion for biomaterials facilitating the formation of epithelial spheroids. Show more

Keywords: HaCaT cells, spheroid formation, atomic force microscope, single-cell adhesion, chitosan

DOI: 10.3233/CH-209217

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-200875

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

Authors: Yüksel, Serkan | Pancar Yüksel, Esra | Meriç, Murat

Article Type: Research Article

Abstract: BACKGROUND: Microvascular dysfunction is one of the pathophysiological mechanisms in heart failure. Nailfold videocapillaroscopy is a noninvasive technique used to examine the microvasculature. OBJECTIVE: In this study; we aimed to investigate the nailfold capillaroscopic abnormalities in heart failure patients with reduced and preserved ejection fraction and compare those with control group. METHODS: Three groups of patients were recruited for the study: HFrEF group includes the patients with heart failure with reduced ejection fraction (HFrEF), HFpEF group, patients with heart failure with preserved ejection fraction (HFpEF) and control group, healthy asymptomatic individuals. Nailfold videocapillaroscopy was performed with …a videodermatoscope and all nailfold images were evaluated for enlargement and hemorrhages. RESULTS: Abnormal videocapillaroscopic findings including enlargement and/or hemorrhages were present in 7 (24%) patients in HFrEF group, 19 (66%) patients in HFpEF group and 11 (37%) in control group. The number of patients with abnormal videocapillaroscopic findings were significantly greater in HFpEF group compared to HFrEF (p  <  0.05) and control groups (p  <  0.05). However, no significant difference was observed in videocapillaroscopic findings between HFrEF and control groups. CONCLUSIONS: Our study showed that microvascular abnormalities demonstrated by videodermatoscopic examination of nailfold capillaries are considerably more common in HFpEF patients compared to HFrEF and control groups. Show more

Keywords: Capillaroscopy, heart failure, heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, nailfold videocapillaroscopy

DOI: 10.3233/CH-200968

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

Authors: Michalik, Katharina | Beyer, Lukas | Zeman, Florian | Wendl, Christina | Rennert, Janine | Fellner, Claudia | Stroszczynski, Christian | Wiggermann, Philipp

Article Type: Research Article

Abstract: Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a hepatocyte-specific, linear ionic contrast agent for MRI. In comparison to other linear contrast agents Gd-EOB-DTPA is excreted equally through liver and kidneys. This prospective longitudinal study investigates the signal intensity (SI) in the dentate nucleus (DN) on unenhanced T1-weighted images after repetitive application of Gd-EOB-DTPA. 46 patients were included into the study and 107 MRI examinations were performed. Statistical analysis of 25 patients showed no significant correlation between cumulative dose of Gd-EOB-DTPA and SI change and between the DN/Pons ratiolast and the mean DN/Pons ratiofirst . Subgroup analysis however revealed a significant correlation …for one out of two readers. Gd-EOB-DTPA deposition could not be proven in the framework of this study. Show more

DOI: 10.3233/CH-209219

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

Authors: Xian, Meng-Fei | Pan, Kang-Ming | Zhang, Jian-Chao | Cheng, Mei-Qing | Huang, Hui | Chen, Li-Da | Zhao, Zhen-Xian | Wang, Wei

Article Type: Research Article

Abstract: Tumor-induced osteomalacia (TIO) is a vanishingly rare paraneoplastic syndrome which is usually caused by phosphaturic mesenchymal tumors (PMTs). The conventional treatment for PMTs is total resection, and ultrasound-guided radiofrequency ablation (RFA) can also be used for the treatment of PMTs patients, especially for patients in whom complete resection may lead to serious complications. We report two cases with PMT who presented syndrome with progressive musculoskeletal complaints and performed ultrasound-guided biopsy and RFA. Ultrasound-guided RFA, which is a safe and effective minimally invasive treatment option, appears to be a valuable alternative to surgery for patients presenting with PMT. We are the …first reported case of RFA guided by ultrasonography in the treatment of PMT. Show more

Keywords: Tumor-induced osteomalacia, oncogenic osteomalacia, phosphaturic mesenchymal tumor, radiofrequency ablation, ultrasound

DOI: 10.3233/CH-200921

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

Authors: Schwarze, V. | Marschner, C. | Negrão de Figueiredo, G. | Rübenthaler, J. | Clevert, D.-Á.

Article Type: Research Article

Abstract: BACKGROUND: Popliteal artery aneurysms (PAA) are the most common peripheral artery aneurysms. Most common cause is arteriosclerosis. Acute thromboembolic limb ischemia and rupture of the PAA depict severe complications. Diagnostic tools for identifying PAAs are (Doppler) ultrasound, CT/MR angiography and DSA. PURPOSE: The aim of the present retrospective single-center study is to assess the application and safety of CEUS for assessing untreated and treated PAAs. MATERIALS AND METHODS: 13 patients were included in this study on whom CEUS was performed between 2007–2016. CEUS examinations were performed and interpreted by an experienced single radiologist (EFSUMB Level 3). …RESULTS: CEUS allowed for the detection of PAAs in all cases. CEUS allowed for detection of partial thrombosis of PAA in 7/8 of untreated patients, proper exclusion of PAA upon femoro-popliteal bypass in 3 patients, incomplete exclusion of PAA upon femoro-popliteal bypass in 1 patient and ruling out of in-stent stenosis in 1 patient. CONCLUSION: CEUS is a useful and safe tool for in real-time evaluation of PAAs in the pre-/post-treatment status. In addition to conventional (Doppler) ultrasound and as an alternative tool to more elaborate imaging modalities, CEUS might be integrated in the future diagnostic work-up and follow-up of PAA patients. Show more

Keywords: Popliteal arterial aneurysm, PAA, arteriosclerosis, ultrasound, CEUS

DOI: 10.3233/CH-209214

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

Authors: Feder, Anna-Lena | Pion, Eric | Troebs, Johannes | Lenze, Ulrich | Prantl, Lukas | Htwe, Maung Maung | Phyo, Aung | Haerteis, Silke | Aung, Thiha

Article Type: Research Article

Abstract: BACKGROUND: Osteosarcomas are a rare, heterogeneous and malignant group of bone tumors that have a high potential for metastasis and aggressive growth patterns. Treatment of metastasized osteosarcoma is often insufficient and research is compromised by problems encountered when culturing cells or analyzing genetic alterations due to the high level of intratumoral and intertumoral heterogeneity. The chick chorioallantoic membrane (CAM) model, a 3D-in-vivo -tumor-model, could potentially facilitate the investigation of osteosarcoma heterogeneity at an individual and highly specified level. OBJECTIVE: Objective was to establish the grafting and transplantation of different primary osteosarcoma tissue parts onto several consecutive CAMs for …tumor profiling and investigation of osteosarcoma heterogeneity. METHODS: Various parts of primary osteosarcoma tissue were grafted onto CAMs and were transplanted onto another CAM for five to seven consecutive times, enabling further experimental analyzes. RESULTS: Primary osteosarcoma tissue parts exhibited satisfactory growth patterns and displayed angiogenic development on the CAM. It was possible to graft and transplant different tumor parts several times while the tissue viability was still high and tumor profiling was performed. CONCLUSIONS: Primary osteosarcoma tissue grew on several different CAMs for an extended time period and neovascularization of serial transplanted tumor parts was observed, improving the versatility of the 3D-in-vivo -tumor-model. Show more

Keywords: Osteosarcoma, sarcoma, cancer, tumor heterogeneity, intratumoral heterogeneity, CAM model, 3D-in-vivo-tumor-model

DOI: 10.3233/CH-209204

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

Authors: Troeltzsch, Daniel | Niehues, Stefan M. | Fluegge, Tabea V. | Neckel, Norbert | Heiland, Max | Hamm, Bernd | Shnayien, Seyd

Article Type: Research Article

Abstract: BACKGROUND: Detecting local tumor recurrence from post-treatment changes in head and neck cancer (HNC) remains a challenge. Based on the hypothesis that post-therapeutically altered tissue is bradytroph, lower perfusion values are expected in perfusion CT (PCT) while higher perfusion values are expected in recurrent malignant tissue. OBJECTIVES: This prospective study investigates PCT for post-treatment recurrent HNC detection with a maximum slope algorithm. METHODS: A total of 80 patients who received PCT of the head and neck for post-therapy follow-up, of which 63 had no tumor recurrence and 17 presented a histopathologically confirmed recurrence were examined. Regions …of interest were placed in the location of the initial tumor, in reference ipsilateral nuchal muscle tissue and the corresponding internal carotid artery. Perfusion was calculated using a single-input maximum slope algorithm. RESULTS: With PCT, recurrent HNC can be differentiated from post-treatment tissue (p  <  0.05). It further allows delineating recurrent tumor tissue from benign nuchal tissue of reference (p  <  0.05). PCT data of patients with and without recurrent HNC are comparable as perfusion values of reference tissues in patients with and without HNC do not differ (p  >  0.05). CONCLUSIONS: PCT in combination with a commercially available maximum slope algorithm offers radiologists a reliable imaging tool to detect recurrent head and neck cancer within post-therapeutically altered tissue. Show more

Keywords: Head and neck cancer, perfusion computed tomography, tumor recurrence

DOI: 10.3233/CH-209209

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

Authors: Kammerer, S. | Stroszczynski, C. | Jung, E.M.

Article Type: Research Article

Abstract: PURPOSE: The aim of our pilot study is to consider if the new flow presentation of the V-flow allows an assessment of the valve morphology of the crosses with respect to an insufficiency. MATERIAL AND METHODS: We performed a total of 50 investigations in which we documented a complete valve closure at the so called “crosse” at the valve of the large saphenous vein, a delayed valve closure or an incomplete valve closure with consecutive insufficiency at the crosse. The valve function of the crosse is crucial for the development of varicosis. For our study we recorded age …and gender of the patients. One patient in the study was suffering from Covid19. For the examinations we used a 3–9 MHz probe and a high-end ultrasound device. The examination was performed in a lying position and under quiet conditions. Before examination we practiced inhalation and exhalation as well as “pressing” or coughing with the patients, which resulted in a physiological closure of the venous valves. To rule out thrombosis, we carried out compression sonography on the legs. During the examination we documented the B-scan, the Color-Coded Duplex Sonography, the HR-flow and the V-flow for 3 seconds at the estuary of the crosses and incorporated these parameters into our measurements. Via V-flow, vectors can be imaged by representing the flow of erythrocytes and visually indicate a possible insufficiency due to delayed or incomplete valve closure. RESULTS: 31 of 50 patients (age 19–81years) showed a complete valve closure of the crosses, while three patients suffered from thrombosis. In eight of the 50 study participants (age 45–79 years) a delayed valve closure could be diagnosed by V-flow within 1–2 seconds. None of them had a thrombosis, but six of them suffered from cancer. In eleven patients we derived an incomplete valve closure with insufficiency (age 51–88 years). With reflux it took >2 seconds to close the valve. The patient with Covid19 also showed an incomplete valve closure with insufficiency. At the same time this patient showed a Covid19-associated deep vein thrombosis. Eight additional patients also had a thrombosis. Six of them suffered from cancer. Overall, the results were best visualized by V-Flow. CONCLUSION: The crosse as a significant venous structure can be well investigated by V-flow with respect to hemodynamic changes and a resulted reflux. Also associated changes close to the valve can be visualized well. Show more

Keywords: Valve insufficiency, crosses, FKDS (color-coded duplex sonography), V-flow

DOI: 10.3233/CH-209205

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

Authors: Nie, Yan | Xu, Xun | Wang, Weiwei | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: BACKGROUND: Keratinocytes are exposed to a thermal gradient throughout epidermal layers in human skin depending on environmental temperatures. OBJECTIVE: Here, the effect of cyclic temperature changes (Δ T) on HaCaT cell behaviors was explored. METHODS: HaCaT cells were cultured at constant temperature (37°C or 25°C) or under Δ T conditions. The morphology, mechanics, cell cycle progression, proliferation, and lipid synthesis of HaCaT cells were determined. RESULTS: Δ T conditions led to the inhomogeneous arrangement of the cytoskeleton in HaCaT cells, which resulted in enlarged size, rounder shape, and increased stiffness. Accumulation in the G2/M …phase in the cell cycle, a decreased proliferation rate, and a delayed lipogenesis were detected in HaCaT cells cultured under Δ T conditions. CONCLUSIONS: Δ T conditions resulted in the re-arrangement of the cytoskeleton in HaCaT cells, which showed similarity to the temperature-induced disassemble and re-assemble of cytoskeletons in keratinocyte in vivo . The altered cytoskeleton arrangement resulted in the cell enlargement and stiffening, which reflected the changes in cellular functions. The application of oscillatory temperature in the in vitro culture of keratinocytes provides a way to gain more insights into the role of skin in response to environmental stimuli and maintaining its homeostasis in vivo . Show more

Keywords: Oscillatory temperature, HaCaT cells, mechanics, morphology, proliferation

DOI: 10.3233/CH-209208

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

Authors: Schwarze, V. | Marschner, C. | Völckers, W. | Negrão de Figueiredo, G. | Rübenthaler, J. | Clevert, D.-Á.

Article Type: Research Article

Abstract: BACKGROUND: HCC is the most frequent primary liver cancer entity. Major risk factors comprise chronic HBC and HCV infections, ALD or NAFLD. Apart from the anamnesis, the clinical examination and serologic analysis, an essential part of the diagnostic HCC work-up is due to imaging findings from sonography, CT or MRI scans. HCC lesions feature a distinct vascularization pattern: hyperenhancement during early arterial and hypoenhancement/wash-out during portal venous or delayed phases. CEUS facilitates dynamic assessment of microperfusion patterns of suspicious liver lesions. PURPOSE: The purpose of the present retrospective single-center study was to determine the diagnostic value of CEUS …for assessing HCC by comparison with findings from MRI scans. MATERIALS AND METHODS: Between 2004-2018 292 patients with suspicious liver lesions underwent CEUS and MRI. All patients underwent native B-mode, Color Doppler and CEUS after given informed consent. The applied contrast agent was a second-generation blood pool agent (SonoVue ®, Bracco, Milan, Italy). Every CEUS examination were performed and interpreted by a single experienced radiologist (EFSUMB Level 3). RESULTS: CEUS was performed on all included patients without occurrence of any adverse effects. CEUS showed a sensitivity of 96%, a specificity of 91%, a PPV of 95% and a NPV of 94% for analyzing HCC in comparison with MRI as the diagnostic gold standard. CONCLUSION: With a distinguished safety profile CEUS shows a high diagnostic accuracy in assessing HCC compared to corresponding results from MRI scans. Show more

Keywords: Hepatocellular cancer, HCC, liver, CEUS, MRI

DOI: 10.3233/CH-209213

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

Authors: Bitterer, Florian | Hornung, Matthias | Platz Batista da Silva, Natascha | Schlitt, Hans J. | Stroszczynski, Christian | Wege, Anja K. | Jung, Ernst-Michael

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the diagnostic accuracy of high-resolution ultrasound (HRU) for the detection of hepatic metastases of breast cancer in a humanized tumour mouse (HTM) using clinical standard technology. In addition, the efficiency of standard contrast-enhanced ultrasound (CEUS) [microbubbles of sulphur hexafluoride] and CEUS using a novel VEGFR2-targeted contrast agent [BR55 ® ] was examined. METHODS: A total of 14 HTM were sonographically examined twice. In addition to a human immune system, the animals developed hepatic tumour lesions after intrahepatic injection of BT-474 breast cancer cells. Digital cine loops from the arterial phase (15–35 sec), the portal venous phase (35–90 sec) …and the late phase (3–15 min) of the entire liver were analysed. Data were correlated to histopathology. RESULTS: After 9 months, half of the mice (7/14) revealed the development of hepatic breast cancer metastases. The detection limit was 1 mm tumour diameter. In particular, the use of targeted contrast media reduced the needed tumour diameter and helped to precisely classify tumour tissue. In 93% (13/14), the findings of ultrasound could be approved by histological examination by the pathologist. CONCLUSIONS: This study in HTM demonstrated the high feasibility of tumour specific contrast media and standard HRU contrast agents to detect early liver metastases. Show more

Keywords: Abdomen, contrast-enhanced ultrasound (CEUS), BR55 ® , SonoVue ® , humanized tumour mice (HTM)

DOI: 10.3233/CH-200898

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

Authors: Rickert, Dorothee | Steinhart, Helmut | Lendlein, Andreas

Article Type: Research Article

Abstract: BACKGROUND: The pharyngeal reconstruction is a challenging aspect after pharyngeal tumor resection. The pharyngeal passage has to be restored to enable oral alimentation and speech rehabilitation. Several techniques like local transposition of skin, mucosa and/or muscle, regional flaps and free vascularized flaps have been developed to reconstruct pharyngeal defects following surgery, in order to restore function and aesthetics. The reconstruction of the pharynx by degradable, multifunctional polymeric materials would be a novel therapeutical option in head and neck surgery. MATERIALS AND METHODS: Samples of an ethylene-oxide sterilized polymer (diameter 10 mm, 200μ m thick) were implanted for the reconstruction …of a standardized defect of the gastric wall in rats in a prospective study. The stomach is a model for a “worst case” application site to test the stability of the implant material under extreme chemical, enzymatical, bacterial, and mechanical load. RESULTS: Fundamental parameters investigated in this animal model were a local tight closure between the polymer and surrounding tissues, histological findings of tissue regeneration and systemic responses to inflammation. A tight anastomosis between the polymer and the adjacent stomach wall was found in all animals after polymer implantation (n  = 42). Histologically, a regeneration with glandular epithelium was found in the polymer group. No differences in the systemic responses to inflammation were found between the polymer group (n  = 42) and the control group (n  = 21) with primary wound closure of the defect of the gastric wall. CONCLUSIONS: A sufficient stability of the polymeric material is a requirement for the pharyngeal reconstruction with implant materials. Show more

Keywords: Oncological head and neck surgery, pharyngocutaneous fistulae, multifunctional polymeric materials, reconstruction of pharyngeal defects, animal model

DOI: 10.3233/CH-209212

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

Authors: Lutze, Stine | Riebe, Helene | Jünger, Michael | Arnold, Andreas

Article Type: Research Article

Abstract: While Kaposi’s Sarcoma (KS) was common in the 1980s and early 1990s in HIV-positive patients and one of the most common AIDS-defining diseases, its prevalence today has decreased significantly due to the early and widespread use of chimeric antigen receptor T-cell (cART) therapy. The rapid initiation of cART or, if occurring during ongoing cART, an optimization of antiretroviral therapy leads to a healing of this tumour disease in most patients. The aim of the therapy is immune reconstitution, as the immunodeficiency resulting from the HIV disease (reduced CD4+-T helper cells) promotes the development and spread of KS. This case report …describes the course of KS in the first diagnosis of AIDS in a 36-year-old patient. The HIV copy count was below the detection limit and the CD3+/CD4+ T-helper cell count was only slightly below the normal value in the six-month follow-up after initial diagnosis and initiation of cART therapy. However, the clinical findings in the one-year follow-up showed only a partial response, whereby it was noted that new tumour lesions also developed focally in addition to individual progressive lesions. This was demonstrated clinically, dermatoscopically and by laser Doppler fluxmetry measurements of the lesions. Such a progression was observed in about one-third of the patients affected in various studies and is called Immune Reconstitution Inflammatory Syndrome. Other therapies in addition to cART are necessary here to suppress this immunological phenomenon (including cytostatic drugs). Promising studies are currently underway, including utilising checkpoint inhibitors. These are of great therapeutic interest due to the high immunological activity of KS itself and usually of systemic inflammatory response syndrome. Show more

DOI: 10.3233/CH-209203

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2020

Authors: Krüger-Genge, A. | Jung, F. | Hufert, F. | Jung, E.-M. | Küpper, J.-H. | Storsberg, J.

Article Type: Research Article

Abstract: Thrombotic events result from different pathologies and are the underlying causes of severe diseases like stroke or myocardial infarction. Recent basic research now revealed a link between food uptake, food conversion and gut metabolism. Gut microbial production of trimethylamine N-oxide (TMAO) from dietary nutrients like choline, lecithin and L-carnitine was associated with the development of cardiovascular diseases. Within this review we give a systematic overview about the influence of TMAO on blood components like platelets and endothelial cells which both are involved as key players in thrombotic processes. In summary, a mechanistic correlation between the gut microbiome, TMAO and cardiovascular …diseases becomes obvious and emphasizes to the significance of the intestinal microbiome. Show more

Keywords: Microbiome, trimethylamin-N-oxide, platelets, endothelial cells, atherosclerosis

DOI: 10.3233/CH-209206

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

Authors: Curio, Jonathan | Abulgasim, Kamal | Kasner, Mario | Rroku, Andi | Lauten, Alexander | Lendlein, Andreas | Landmesser, Ulf | Reinthaler, Markus

Article Type: Research Article

Abstract: BACKGROUND: Transesophageal echocardiography (TEE) as a guiding tool for edge-to-edge transcatheter tricuspid valve repair (EETVr) using MitraClip (Abbott Vascular, Santa Clara, USA) may not offer sufficient image quality in a significant proportion of patients. OBJECTIVES: Intracardiac echocardiography (ICE) as additional guiding tool in EETVr with the MitraClip device. METHODS: Appropriate angulations of the ICE catheter to visualize each commissure of the tricuspid valve were established in 3D printed heart models. In a single tertiary-care center ICE was used to support EETVr as additional guidance when TEE image quality was insufficient. Procedural safety and outcomes up to …30-days were compared between ICE/TEE and TEE only guided patients. RESULTS: In 6 of 11 patients (54.5%) undergoing EETVr with MitraClip TEE alone was unsatisfactory, necessitating additional ICE guidance. In 4 of these 6 patients ICE enabled a successful completion of the procedure. The steering maneuvers identified in the 3D models were well applicable in all patients, providing examples for potential future ICE implementation in EETVr. Under both TEE alone (n  = 5) and ICE (n  = 6) guidance the rate of procedural complications was 0%. According to vena contracta values at discharge significant TR reduction was achievable in the treated cohort (p  = 0.011). At 30-days follow-up one patient (ICE guided) died following global heart failure, not associated with the procedure itself. CONCLUSIONS: ICE guidance may offer an additional tool to guide EETVr with the MitraClip device in patients with poor TEE quality, as it enables successful results without impairing procedural safety. Show more

Keywords: Intracardiac ultrasound, tricuspid regurgitation, transcatheter tricuspid valve repair, edge-to-edge repair

DOI: 10.3233/CH-209211

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

Authors: Lonic, Daniel | Heidekrueger, Paul I. | Bosselmann, Talia | Niclas Broer, P. | Gertler, Ralph | Wolfgang Martin, Klaus | Prantl, Lukas | Ninkovic, Milomir | Giunta, Riccardo | Ehrl, Denis

Article Type: Research Article

Abstract: BACKGRUND: The coagulation status of burn patients is generally impaired and is a major factor of the deteriorating burn patients’ overall situation. In trauma and other patient groups, the differential diagnosis of coagulation impairment has been largely improved by the use of rotational thromboelastometry (ROTEM®). The aim of this prospective observational study was the differentiated observation of coagulopathy in severely burned patients using standard parameters and ROTEM® thrombelastometry during the relevant stages of burn disease. PATIENTS AND METHODS: Twelve patients that sustained at least 20% third degree burns of total body surface area (TBSA) were included in the …study. Standard and ROTEM® coagulation analyses were performed on admission and then twice daily during the first 14 days following burn trauma. RESULTS: Although the initial assessment of DIC was similar for both standard labs and ROTEM® measurements, more patients were detected to be in a state of worsening coagulation status for a longer time in ROTEM® than in standard measurements. In addition, one patient was rated in to be in decompensated DIC for 3 days according to ROTEM® measurements, while no patient was rated to be in a decompensated DIC based on standard parameters. CONCLUSION: This study points towards a more complex picture and higher occurrence of DIC in burn patients when thrombelastometric measurements like ROTEM® are taken into account in addition to standard coagulation parameters. Show more

Keywords: Thrombelastometry, coagulation, burn injury

DOI: 10.3233/CH-209210

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

Authors: Fu, Tiantian | Ding, Hong | Xu, Chen | Zhu, Yuli | Xue, Liyun | Lin, Feng

Article Type: Research Article

Abstract: BACKGROUND: Fibrolamellar hepatocellular carcinoma (FLHCC) is an unusual variant of hepatocellular carcinoma (HCC). Revealing the imaging features is important to the diagnosis of FLHCC. OBJECTIVE: The aim of this study was to investigate the imaging characteristics of FLHCCs. METHODS: This retrospective study included 29 patients with histopathologically proved FLHCC and 96 patients proved HCC. All patients underwent an ultrasound examination pre-operation. RESULTS: The average maximum diameters of the FLHCC and HCC lesions were 7.4±4.1 cm and 4.1±3.0 cm, respectively. On the ultrasound, 79.3% of the FLHCCs and 12.3% of the HCCs showed the internal hyperechoic area; …48.3% of the FLHCCs and 3.3% of the HCCs displayed a strip-like attenuation. Calcification was noted in 20.7% of the FLHCCs, while none in HCCs. On the contrast-enhanced ultrasound (CEUS), all FLHCC lesions and 87.7% of the HCCs displayed hyperenhancement in the arterial phase. An internal, unenhanced central scar appeared in all FLHCCs, while none in HCCs. CONCLUSIONS: The ultrasonographic features of FLHCC lesions indicate that they are relatively large masses showing the internal hyperechoic area or strip-like attenuation or calcification on the US and hypervascularity with an unenhanced central scar on the CEUS as compared with conventional HCC lesions. Show more

Keywords: Carcinoma, hepatocellular, contrast media, ultrasonography, diagnosis

DOI: 10.3233/CH-200896

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

Authors: Fokam, Danielle | Aali, Maral | Dickson, Kayle | Scott, Cassidy | Holbein, Bruce | Zhou, Juan | Lehmann, Christian

Article Type: Research Article

Abstract: BACKGROUND: Sepsis is the result of a dysregulated host immune response to an infection. An ideal therapy would target both, the underlying infection and the dysregulated immune response. DIBI, a novel iron-binding polymer, was specifically developed as an antimicrobial agent and has also demonstrated in vivo anti-inflammatory properties. OBJECTIVE: This study aimed to further investigate the effects of DIBI with and without the antibiotic imipenem (IMI) in colon ascendens stent peritonitis (CASP)-induced experimental sepsis. METHODS: Vehicle, DIBI and/or IMI were administered in C57BL/6 mice after CASP surgery. Intestinal leukocyte activation and capillary perfusion was evaluated …by intravital microscopy. Moreover, bacterial load in peritoneal lavage fluid and blood, and plasma cytokine levels were assessed. In a second series of experiments, surgery to repair the colon was performed at 5 hr and these mice were followed for long-term survival over 7 days. RESULTS: DIBI reduced leukocyte adhesion, improved capillary blood flow, and decreased key plasma cytokines levels. DIBI also improved survival of infected mice, and greatly improved IMI efficacy. Survivors treated with IMI and DIBI were found to be free of systemic infection. CONCLUSIONS: DIBI has promising potential for sepsis treatment including its use as a sole or an adjunct therapeutic with antibiotics. Show more

DOI: 10.3233/CH-209207

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-21, 2020

Authors: Bruno, Raphael Romano | Schemmelmann, Mara | Wollborn, Jakob | Kelm, Malte | Jung, Christian

Article Type: Research Article

Abstract: OBJECTIVE: Diagnostic and risk stratification in intensive and emergency medicine must be fast, accurate, and reliable. The assessment of sublingual microcirculation is a promising tool for this purpose. However, its value is limited because the measurement is time-consuming in unstable patients. This proof-of-concept validation study examines the non-inferiority of a reduced frame rate in image acquisition regarding quality, measurement results, and time. METHODS: This prospective observational study included healthy volunteers. Sublingual measurement of microcirculation was performed using a sidestream dark field camera (SDF, MicroVision Medical®). Video-quality was evaluated with a modified MIQS (microcirculation image quality score). AVA 4.3C …software calculated microcirculatory parameters. RESULTS: Thirty-one volunteers were included. There was no impact of the frame rate on the time needed by the software algorithm to measure one video (4.5 ± 0.5 minutes) for AVA 4.3C. 86 frames per video provided non inferior video quality (MIQS 1.8 ± 0.7 for 86 frames versus MIQS 2.2 ± 0.6 for 215 frames, p  < 0.05), equal results for all microcirculatory parameters, but did not result in an advantage in terms of speed. No complications occurred. CONCLUSION: Video captures with 86 frames offer equal video quality and results for consensus parameters compared to 215 frames. However, there was no advantage regarding the time needed for the overall measurement procedure. Show more

Keywords: Microcirculation, risk-stratification, SDF-imaging, point-of-care measurement

DOI: 10.3233/CH-209201

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

Authors: Yang, Juesheng | Hu, Shan | Huang, Li | Zhou, Jianliang | Xiang, Haiyan | Yang, Heng | Cheng, Hongzhang | Tang, Yanhua

Article Type: Research Article

Abstract: BACKGROUND: Transient receptor potential channel 7 (TRPM7) plays an important role in maintaining intracellular ion concentration and osmotic pressure. OBJECTIVE: The purpose of this study was to investigate the role and mechanism of inhibiting the expression of TRPM7 in the treatment of distal myocardial ischemia. METHODS: H9C2 cells were treated with hypoxia post-treatment and reperfusion, respectively, detect the expression of HIF-1α and TRPM7, the concentration of Ca2 + and the degree of apoptosis in the H9C2 cells. The relevant miRNAs targeting TRPM7 were searched, the TRPM7 interference vectors were constructed, and the interference of different …interference vectors on TRPM7 in H9C2 cells was detected. RESULTS: The results showed that hypoxia post-treatment treatment would lead to increased expression of miR-22-3p which directly targeting TRPM7, decreased expression of TRPM7, increased expression of HIF-α and increased intracellular Ca2 + concentration. While reperfusion can increase the expression of HIF-1α and TRPM7 in H9C2 cells and increase the degree of apoptosis. CONCLUSION: Knockdown of TRPM7 can significantly reduce reperfusion injury in H9C2 cells, reduce the degree of apoptosis, and the TRPM7 interference vector can inhibit the expression of TRPM7 and have a certain protective effect on the reperfusion injury of H9C2 cells. Show more

Keywords: TRPM7, hypoxia post-treatment, protective effect, H9C2 cardiomyocytes

DOI: 10.3233/CH-200934

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2020

Authors: Grambow, Eberhard | Klee, Gina | Xie, Wentao | Schafmayer, Clemens | Vollmar, Brigitte

Article Type: Research Article

Abstract: INTRODUCTION: The volatile endogenous mediator hydrogen sulfide (H2 S) is known to impair thrombus formation by affecting the activity of human platelets. Beside platelets and coagulation factors the endothelium is crucial during thrombogenesis. OBJECTIVE: This study evaluates the effect of the H2 S donor GYY4137 (GYY) on human umbilical vein endothelial cells (HUVECs) in vitro . METHODS: Flow cytometry of resting, stimulated or GYY-treated and subsequently stimulated HUVECs was performed to analyse the expression of E-selectin, ICAM-1 and VCAM-1. To study a potential reversibility of the GYY action, E-selectin expression was further assessed on HUVECs that …were stimulated 24 h after GYY exposure. A WST-1 assay was performed to study toxic effects of the H2 S donor. By using the biotin switch assay, protein S-sulfhydration of GYY-exposed HUVECs was assessed. Further on, the effects of GYY on HUVEC migration and von Willebrand factor (vWF) secretion were assessed. RESULTS: GYY treatment significantly reduced the expression of E-selectin and ICAM-1 but not of VCAM-1. When HUVECs were stimulated 24 h after GYY treatment, E-selectin expression was no longer affected. The WST-1 assay revealed no effects of GYY on endothelial cell viability. Furthermore, GYY impaired endothelial migration, reduced vWF secretion and increased protein S-sulfhydration. CONCLUSIONS: Summarizing, GYY dose dependently and reversibly reduces the activity of endothelial cells. Show more

Keywords: Thrombosis, E-selectin, S-sulfhydration, migration, gaseous transmitter

DOI: 10.3233/CH-200868

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

Authors: Konschake, Wolfgang | Haase, Hermann | Jünger, Michael | Lutze, Stine | Arnold, Andreas

Article Type: Research Article

Abstract: BACKGROUND: Dermatoscopy is successfully used for the early diagnosis of suspicious skin lesions, however, correct diagnosis depends on training. There is evidence that wavelet analysis by Laser Doppler flowmetry (LDF) can identify malignant melanomas by their hypervascularization and changes in the capillary morphology. OBJECTIVE: To show the capability of LDF in the distinction of melanomas and benign pigmented skin lesions based on data collected over 16 years. METHODS: Evaluation of pigmented skin lesions was based on clinical information. The LDF measurements were taken. The suspect lesion was excised afterwards for histological work-up. Four case reports are …presented. Data collected over 16 years was processed into a neuronal network to estimate the dignity of the lesion. RESULTS: A total of 517 suspicious lesions were analyzed by LDF. In the histological work-up, 114 lesions turned out to be melanomas, whereas 403 benign naevi were secured. Specificity to detect melanomas was good based on the clinical information. The LDF increases the sensitivity of melanoma detection, which is also illustrated in four case reports. CONCLUSION: In addition to clinical parameters, such as color and border, information from the LDF can help in the diagnosis of malignant melanomas. The LDF provides information on the vascularization of the skin lesion. Show more

DOI: 10.3233/CH-200876

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

Authors: Li, Xiao-Long | Xie, Chen-Yi | Xu, Hui-Xiong

Article Type: Research Article

Abstract: Pseudoaneurysm (PSA) formation is the most common arterial complication of endovascular procedures requiring arterial puncture. The present study reported a case of a 72-year-old male patient with iatrogenic femoral artery PSA treated with contrast-enhanced ultrasound (CEUS) - guided thrombin injection. Conventional ultrasound (US) and CEUS were used to diagnose, guide treatment, and evaluate the treatment efficacy. In the case, the PSA was successfully occluded with 1000 IU of thrombin. During the follow-up after 48 hours of thrombin injection, US found that the PSA had complete thrombosis without arterial supply. No complications occurrence in the course of the treatment. CEUS - …guided thrombin injection for the treatment of PSA was effective and safety and the associated literatures were also reviewed. Show more

DOI: 10.3233/CH-200923

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

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

Article Type: Research Article

Abstract: BACKGROUND: The optimal timing of remote ischemic preconditioning (RIPC) in renal ischemia-reperfusion (I/R) injury is still unclear. We aimed to compare early- and delayed-effect RIPC with hematological, microcirculatory and histomorphological parameters. METHODS: In anesthetized male CrI:WI Control rats (n  = 7) laparotomy and femoral artery cannulation were performed. In I/R group (n  = 7) additionally a 45-minute unilateral renal ischemia with 120-minute reperfusion was induced. The right hind-limb was strangulated for 3×10 minutes (10-minute intermittent reperfusion) 1 hour (RIPC-1 group, n  = 7) or 24 hour (RIPC-24 group, n  = 6) prior to the I/R. Hemodynamic, hematological parameters and organs’ surface microcirculation …were measured. RESULTS: Control and I/R group had the highest heart rate (p  < 0.05 vs base), while the lowest mean arterial pressure (p  < 0.05 vs RIPC-1) were found in the RIPC-24 group. The highest microcirculation values were measured in the I/R group (liver: p  < 0.05 vs Control). The leukocyte count increased in I/R group (base: p  < 0.05 vs Control), also this group’s histological score was the highest (p  < 0.05 vs Control). The RIPC-24 group had a significantly lower score than the RIPC-1 (p  = 0.0025 vs RIPC-1). CONCLUSION: Renal I/R caused significant functional and morphological, also in the RIPC groups. According to the histological examination the delayed-effect RIPC method was more effective. Show more

Keywords: Acute kidney injury, ischemia-reperfusion, remote ischemic preconditioning, microcirculation, histopathology

DOI: 10.3233/CH-200916

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

Authors: Zhang, Xifeng | Yang, Likun | Xu, Guixia

Article Type: Research Article

Abstract: OBJECTIVE: Acute myeloid leukemia (AML) is a hematological malignancy. This study was attempted to uncover the effects of long noncoding RNA taurine-upregulated gene1 (TUG1) on the viability and apoptosis of AML cells. METHODS: QRT-PCR was implemented to examine the expression of TUG1, miR-221-3p and KIT in AML. The correlation between TUG1 and clinicopathological features of AML patients was evaluated. The effect of TUG1 on AML cells were studied by RNA interference approach. AML cells were transfected with miR-221-3p mimic and miR-221-3p inhibitor, respectively. Then the viability and apoptosis of AML cells were examined by MTT and flow cytometry …assay, respectively. Additionally, dual-luciferase reporter assay was used to confirm the interactions among TUG1, miR-221-3p and KIT. Western blot was applied to analyze protein expression of KIT. RESULTS: The expression of TUG1 and KIT was up-regulated in AML, but miR-221-3p was down-regulated. TUG1 expression had obviously correlation with World Health Organization (WHO) grade in AML patients. The functional experiment stated that TUG1 silencing suppressed the viability and accelerated the apoptosis of AML cells. Moreover, the mechanical experiment demonstrated that TUG1 and KIT were both targeted by miR-221-3p with the complementary binding sites at 3’UTR. Up-regulation of miR-221-3p inhibited the protein expression of KIT. Furthermore, in the feedback experiment, miR-221-3p inhibition or KIT overexpression reversed the repression of tumor behavior induced by TUG1 silencing. CONCLUSIONS: TUG1 silencing retarded viability and promoted apoptosis of AML cells via regulating miR-221-3p/KIT axis, providing a potential therapeutic target for AML. Show more

Keywords: Acute myeloid leukemia, long noncoding RNA TUG1, microRNA-221-3p, KIT, viability

DOI: 10.3233/CH-200906

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

Authors: Basarici, Ibrahim | Özen, Nur | Kilavuz, Ece | Kısak, Fatih | Basrali, Filiz | Yaras, Nazmi | Koksoy, Sadi | Celik, Mukadder Levent | Ulker, Pinar

Article Type: Research Article

Abstract: BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease characterized with alterations in pulmonary vasculature yielding increased pulmonary arterial resistance. Emerging evidences suggest important regulatory roles of red blood cells (RBCs) on nitric oxide (NO) bioavailability, mainly by modulating their endothelial nitric oxide synthase (eNOS) enzyme activity. OBJECTIVE: The aim of the present study was to evaluate the alterations in RBC eNOS activity and intracellular NO generation under PAH conditions and the modulatory effects of Rho-Kinase (ROCK) inhibitors. METHODS: RBCs were isolated from patients with PAH and age-matched healthy subjects and were analyzed for their eNOS …activity and NO generation capacity under the conditions of the presence or absence of ROCK inhibitor, fasudil. Phosphotidylserine (PS) exposure was also defined. RESULTS: eNOS activity and intracellular NO generation were found to be lower in RBC from PAH patients. ROCK inhibitor increased basal eNOS activity and NO generation capacity of RBC from PAH patients to healty conditions.PS exposure levels were also higher in RBC from PAH patients. CONCLUSIONS: This study provides first evidences for decreased RBC eNOS activity due to its ROCK mediated negative regulation under PAH conditions. Considering increased ROCK activity contributes to progression of PAH, ROCK inhibition influences NO bioavailability through RBC eNOS, in addition to endothelial eNOS. Show more

Keywords: Pulmonary hypertension, eNOS, red blood cell, Rho kinase, fasudil

DOI: 10.3233/CH-200892

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

Authors: Huang, Hui | Li, Manying | Pan, Jiamin | Tong, Wenjuan | Cheng, Meiqing | Liang, Jinyu | Zheng, Yanling | Xie, Xiaoyan

Article Type: Research Article

Abstract: BACKGROUND: Primary hyperparathyroidism (PHPT) results from excessive secretion of parathyroid hormone from parathyroid tumors. Differentiating parathyroid tumors can be challenging before operation. OBJECTIVES: To differentiate parathyroid carcinoma from benign tumors in patients with PHPT by the application of ultrasound and biochemical parameters. METHODS: This study is a retrospective study. The study enrolled 17 patients with parathyroid carcinoma (PC) and 57 patients with parathyroid adenoma (PA), confirmed by postoperative pathology, between September 2010 and July 2017. This study retrospectively compared the ultrasonic features of the tumors included echotexture, maximum lesion diameter, shape, margin, blood flow inside the …mass, intralesional calcifications, cysts in the mass, and biochemical parameters included serum calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphatase (ALP) levels, gender distribution and age of patients between patients with PC and those with PA. RESULTS: In the US images, the two groups showed significant differences in heterogeneity, the appearance of a taller-than-wide shape, irregular or lobulated margins, and intralesional calcifications (p  <  #x003C;<  #x200A;0.05). However, no significant difference was found in echogenicity, maximum lesion diameter, blood flow, and cystic components of the mass (p  >  #x003E;>  #x200A;0.05). The mean PTH levels were significantly different between the two groups (p  <  #x003C;<  #x200A;0.05). The PC and PA patients did not differ significantly in terms of mean serum calcium, mean serum phosphorus, and mean ALP levels (p  >  #x003E;>  #x200A;0.05). There were significant differences to distinguish PC from PA in calcifications in mass or/and taller-than-wide shape combine with PTH >  #x003E;>  #x200A;1000 pg/mL (p  <  #x003C;<  #x200A;0.05). Significant difference existed in the age between the two groups (p  <  #x003C;<  #x200A;0.001). No significant difference existed in the gender distribution between the two groups (p  >  #x003E;>  #x200A;0.05). CONCLUSION: Ultrasound features especially intralesional calcifications and taller-than-wide shape combine with an extremely high serum PTH (>1000 pg/mL) are helpful in differentiating between benign and parathyroid tumors in patients with PHPT. Show more

Keywords: Adenoma, biochemical findings, parathyroid carcinoma, primary hyperparathyroidism, ultrasonography

DOI: 10.3233/CH-200846

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

Authors: Zhang, Wei-Bing | Li, Jing-Jing | Chen, Xiang-Yong | He, Bei-Li | Shen, Rong-Hua | Liu, Hua | Chen, Jian | He, Xiao-Fei

Article Type: Research Article

Abstract: OBJECTIVES: To compare the diagnostic efficacy of shear wave elastography (SWE) comnined with ACR TI-RADS categories for malignancy risk stratification of thyroid nodules with interminate FNA cytology. METHODS: The clinical data, sonographic features, ACR TI-RADS grading and shear wave elastography images of 193 patients of surgical pathologically proven thyroid nodules with interminate FNA cytology were retrospectively analyzed. The diagnostic efficacy of ACR TI-RADS categories, the maximum Young’s modulus (Emax) of SWE and the combination of the two were calculated respectively. RESULTS: The ROC curves were drawn using surgical pathology results as the gold standard. The ROC …curves indicated that the cut-off value of ACR TI-RADS and Emax of SWE was TR5 and 41.2 kPa respectively, and the area under the ROC curve (AUC) was 0.864 (95% CI: 0.879–0.934) and 0.858 (95% CI: 0.796–0.920) respectively. The diagnostic sensitivity, specificity and accuracy of ACR TI-RADS was 81.4% (127/156), 84.8% (31/37), and 81.9% (158/193), respectively. That of SWE Emax was 80.8% (126/156), 78.4% (29/37), and 80.3% (155/193), respectively. After SWE combined with ACR TI-RADS, the sensitivity, specificity and accuracy was 94.2% (147/156), 75.7% (28/37), and 90.7% (175/193), respectively. CONCLUSIONS: ACR TI-RADS classification system and shear wave elastography had high diagnostic efficacy for thyroid nodules with interminate FNA cytology. The combination of the two could improve diagnostic sensitivity and accuracy, and could help to differentiate benign and malignant thyroid nodules with interminate FNA cytology. Show more

Keywords: Thyroid nodules, indeterminate, shear wave elastography, ACR TI-RADS

DOI: 10.3233/CH-200893

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

Authors: Römer, Claudia | Fischer, Thomas | Haase, Oliver | Möckel, Martin | Hamm, Bernd | Lerchbaumer, Markus Herbert

Article Type: Research Article

Abstract: BACKGROUND: Median arcuate ligament syndrome (MALS) is a rare condition due to compression of the celiac artery (CA) by an anatomically abnormal median arcuate ligament. With ultrasonography (US) as first-line diagnostic modality in patients with unclear abdominal pain, there is limited data on its diagnostic performance in MALS. OBJECTIVE: To investigate the value of CA peak systolic velocity (PSV) in the workup of patients with suspected MALS. METHODS: Patients with diagnosis of MALS between 2009 and 2019 were referred by Department of Visceral Surgery after clinical and gastroenterological workup. Diagnosis was confirmed by by surgery or …further cross-sectional imaging. B-mode US findings and PSV in the CA during various respiratory states were compared between patients with a final MALS diagnosis and patients not meeting the diagnostic criteria. RESULTS: Patients with proven MALS (n  = 10) had higher median CA PSV during normal inspiratory breath-hold (239 [IQR, 159–327] vs. 138 [IQR, 116–152] cm/s; p  <  #x003C;<  #x200A;0.001), and expiratory breath-hold (287 [IQR, 191–412] vs. 133 [IQR, 115–194] cm/s; p  <  #x003C;<  #x200A;0.001) compared to patients without MALS (n  = 36). CA PSV in both inspiratory breath-hold (AUC 0.88, 95% CI 0.77–1.00) and expiratory breath-hold (AUC 0.89, 95% CI 0.78–1.00) was of diagnostic value for confirming MALS. The best diagnostic performance (100% sensitivity, 80% specificity) was found for the combination of CA PSVexpiration  + 2.4 · PSVinspiration  > 550 cm/s . CONCLUSIONS: Since results on optimal cutoff values are inconsistent, a combination of CA PSVs during breathing maneuvers may help to diagnose or rule out MALS. Show more

Keywords: Median arcuate ligament syndrome, MALS, Dunbar syndrome, color-coded duplex sonography, coeliac artery compression syndrome

DOI: 10.3233/CH-200903

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

Authors: Martini, Romeo

Article Type: Research Article

Abstract: The most important and consulted guidelines dealing with not healing foot ulcers suggest the measurement the foot perfusion (FP) to exclude the critical limb ischemia (CLI) because of the high risk of limb amputation. But the recommended cut-off values of FP fail to include all the heterogeneity of patients of the real-life with a not healing ulcer. Often these patients are diabetics with a moderate PAD but high level of infection. To meet this goal, in 2014, the Society for Vascular Surgery has published the “Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Infection, and foot Ischemia …(WIfI).” This new classification system changed the criteria of assessment of limb amputation risk replacing the single cut-off value role, with a combination of a spectrum of perfusion values along with graded infection and dimension levels of skin ulcers. The impact of this new classification system was remarkable so to propose the substitution of the CLI with the new Critical limb-threatening ischemia (CLTI) that seems to define the limb amputation risk more realistically Show more

DOI: 10.3233/CH-200901

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

Authors: Zhao, Li | Wang, Hao | Li, Shan-Shan | Xin, Feng | Wu, Qi | Li, Zheng-Ye | Ma, Xian-Jun

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to retrospectively analyze the blood protective effect of autologous platelet separation in operations for acute aortic dissection. METHODS: A total of 130 patients with acute aortic dissection were enrolled into the present study. The average age of these patients was 52.962±10.5061 years old. These patients underwent the modified aortic arch replacement with the elephant trunk technique or endovascular aortic exclusion with covered stent. Among these patients, 68 patients who underwent autologous platelet separation were assigned to the platelet separation group, while the remaining patients were assigned to the control group. All operations were performed …under deep hypothermic circulatory arrest. After anesthesia, 1–2 therapeutic doses of autologous platelets were isolated from patients in the platelet separation group, and these platelets were quickly infused back to these patients after heparin was neutralized by protamine at the end of the cardiopulmonary bypass. The preoperative and postoperative indexes in these two groups were compared. RESULTS: There were no statistically significant differences in age, gender, smoking history, drinking history and hypertension history between these two groups. Compared with controls, the transfusion volume of allogeneic platelets in the perioperative period significantly decreased in the platelet separation group (1.919±1.6226 vs. 0.794±1.1789, P  <  #x003C;<  #x200A;0.05), and the use rate of allogeneic platelets also significantly decreased (74.19% vs. 45.59%, P  <  #x003C;<  #x200A;0.05). CONCLUSION: The intraoperative auto transfusion of platelets significantly reduced the volume of allogeneic platelet transfusion after the operation for aortic dissection, which has a significant blood protective effect. Show more

Keywords: Aortic dissection, autologous plateletpheresis, cardiopulmonary bypass, blood conservation, allogeneic platelet transfusions

DOI: 10.3233/CH-200871

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

Authors: Chen, Kailing | Dong, Yi | Zhang, Weibin | Han, Hong | Mao, Feng | Zhang, Qi | Zheng, Zhu | He, Wanyuan | Wang, Wen-Ping

Article Type: Research Article

Abstract: OBJECTIVE: To explore the specific contrast-enhanced ultrasound (CEUS) features of hepatocellular adenomas (HCA) according to their pathological molecular classifications. METHODS & MATERIALS: In this retrospective study, fifty-three histopathologically proved HCA lesions (mean size, 39.7±24.9 mm) were included. Final histopathological diagnosis of HCA lesions were identified by surgical resection (n  = 51) or biopsy (n  = 2) specimens. CEUS imaging features were compared among four subgroups according to World Health Organization (WHO) 2019 pathological molecular classifications standards. Analysis of variance (ANOVA) were used for statistical analysis of continuous variables. Fisher’s exact test were used for categorical variables. The sensitivity (SE), specificity (SP), …and accuracy of CEUS feature in diagnosis of each HCA subtype were calculated and compared. RESULTS: Final histopathological diagnosis included HNF-1α inactivated HCAs (H-HCA, n  = 12), β -catenin activated HCAs (B-HCA, n  = 8), inflammatory HCAs (I-HCA, n  = 31), and unclassified HCAs (U-HCA, n  = 2). During arterial phase of CEUS, all HCAs were hyper-enhanced, 66.6% (8/12) of H-HCAs and 50% (4/8) of B-HCAs displayed complete hyperenhancement, whereas 58.0% (18/31) of I-HCAs showed centripetal filling hyperenhancement pattern (P  = 0.016). Hyper-enhanced subcapsular arteries could be detected in 64.5% (20/31) I-HCAs during early arterial phase. During portal venous and late phase, sustained hyper- or iso-enhancement were observed in 91.7% (11/12) of H-HCAs, while most of I-HCAs (61.3%, 19/31) and B-HCAs (7/8, 87.5%) were hypo-enhanced (P  = 0.000). Central unenhanced areas were most commonly observed in I-HCAs (29.0%, 9/31) (P  = 0.034). CONCLUSION: Depending on its unique imaging features including enhancement filling pattern, hyper-enhanced subcapsular artery and presence of washout, CEUS might provide helpful diagnostic information for preoperative prediction of various HCA molecular subtypes. Show more

Keywords: Hepatocellular adenoma (HCA), contrast-enhanced ultrasound (CEUS), pathological molecular subtype, washout, differentiate

DOI: 10.3233/CH-200899

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

Authors: Bizjak, Daniel A. | Grolle, Andreas | Urena, Javier Antonio Noriega | Bloch, Wilhelm | Deitenbeck, Robert | Grau, Marijke

Article Type: Research Article

Abstract: BACKGROUND: Autologous blood doping (ABD) is applied to improve performance capacity. ABD includes blood donation, red blood cell (RBC) storage at –80°C and re-infusion prior to or during competition. ABD is not directly detectable with current detection techniques. OBJECTIVE: Since cryopreservation is known to affect RBC physiology in vitro , the aim of the study was to examine whether these alterations are detectable in vivo . METHODS: Blood from six healthy male donors was transferred into conventional blood bags, cryopreserved, stored for 18 weeks at –80°C and re-infused with a RBC volume corresponding to ∼4% of …total blood volume into respective donor. RBC physiology parameters were measured before blood donation/re-infusion, and 0/1/2/6/24/48/72 h and 1 w post re-infusion. RESULTS: RBC parameters and age markers were unaffected during intervention. RBC deformability increased from pre-blood-sampling to pre-re-infusion while deformability and viscosity values remained unaltered post re-infusion. RBC nitric oxide associated analytes, metabolic parameters and electrolyte concentrations remained unaffected. CONCLUSIONS: The data of this pilot study indicate that the increase in RBC deformability might be related to neoformation of RBC after blood donation. The lack of changes in tested parameters might be related to the low re-infused RBC volume which might explain differences to in vitro results. Show more

Keywords: Anti-doping, hemorheology, transfusion, blood storage, autologous blood doping, blood boosting

DOI: 10.3233/CH-200887

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

Authors: Blaha, M. | Langrova, H. | Blaha, V. | Andrys, C. | Stepanov, A. | Lanska, M. | Vejrazkova, E. | Dlouha, D. | Loefflerova, V. | Studnicka, J. | Kostal, M.

Article Type: Research Article

Abstract: BACKGROUND + OBJECTIVE: Age-related macular degeneration (AMD) is the most common cause of practical blindness in people over 60 years of age in industrialised countries. We formulated a hypothesis that a group of initial laboratory parameters would be suitable for prediction of prognosis of AMD, allowing for individual modifications in treatment intensity. PATIENTS AND METHODS: 66 patients with dry form of AMD were treated using rheohaemapheresis with an individual follow-up period of more than 5 years. The patients’ initial laboratory data was split in two subgroups based on treatment success and analysed using discriminant analysis (analysis of the linear and …quadratic models using the automated and interactive step-wise approach) by means of the Systat 13 software. RESULTS: Prediction of prognosis based on the initial laboratory parameters was correct in 79% of unsuccessfully treated patients, allowing for early detection of high-risk patients. With the use of a quadratic model, the prediction was correct in 100% of unsuccessfully treated patients and in 75% of successfully treated patients. CONCLUSION: Implementation of discriminant analysis is a promising method for prediction of prognosis, especially when the patient is at risk of AMD progression, which allows for early and more intensive monitoring and treatment. Show more

Keywords: Rheohaemapheresis, age-related macular degeneration, treatment failure, prognosis prediction

DOI: 10.3233/CH-209101

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

Authors: Kükrek, Haydar | Aitzetmüller, Matthias | Vodiškar, Mateja | Moog, Philipp | Machens, Hans-Günther | Duscher, Dominik

Article Type: Research Article

Abstract: INTRODUCTION: Adipose derived Stem Cells (ASCs) have been proven to play a key role in tissue regeneration. However, exposure to large amounts of cigarette smoke can drastically diminish their function. Erythropoetin (EPO), can modulate cellular response to injury. Therefore, we investigated the ability of EPO to restore the regenerative function and differentiation capacity of ASCs. MATERIAL AND METHODS: Human ASCs were isolated from abdominoplasty samples using standard isolation procedures. Cell identity was established by means of Fluorescence Activated Cell Scanning. Subsequently, isolated ASCs were cultivated with cigarette smoke extract both with and without EPO. Parameters investigated included - …cellular metabolic activity, adipogenic and osteogenic differentiation capacity, and in vitro wound closure capacity. For further enhancing wound closure, EPO was combined with Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) or Stromal Derived Factor-1 alpha (SDF-1 a). RESULTS: Cigarette smoke reduces adipogenic differentiation, the osteogenic differentiation capacity as well as the in vitro wound healing ability of human derived ASCs. EPO did not change metabolic activity of ASCs significantly. The addition of EPO could partially restore their function. The combination of EPO with GM-CSF or SDF-1did not result in a synergistic effect regarding wound healing ability. CONCLUSION: Exposure to cigarette smoke significantly reduced the regenerative potential of ASCs. Treatment of ASCs exposed to cigarette smoke with EPO has the potential to partially restore their function. Show more

Keywords: Mesenchymal stem cells, erythropoietin, cigarette smoke extract, wound healing, ASC

DOI: 10.3233/CH-200852

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

Authors: Wu, Yongjuan | Cheng, Guangyuan | Chen, Hui | Wang, Jingzhong | Wang, Jiangtao | Wang, Wanbi

Article Type: Research Article

Abstract: OBJECTIVE: IL-17 is considered to be a cancer-promoting gene in hepatocellular carcinoma (HCC). Here, we explored the effect of IL-17 in predicting the therapeutic effect of transcatheter arterial chemoembolization (TACE) combined with apartinib in patients with HCC in this study. METHODS: Established of IL-17 knockdown SK-Hep1 cells for studying the effects of IL-17 expression on the invasion and migration of human HCC cells in vitro by transwell assay and tumor angiogenesis in nude mouse. Immunohistochemistry was used to detect the expression of IL-17, E-cadherin, Vimentin and CD34 protein in 175 cases of human HCC tumor tissues. Kaplan-Meier …was used to analyze the prognostic significance of TACE combined with apatinib treatment in HCC patients. RESULTS: n SK-Hep1 cells, IL-17 knockdown could increase E-cadherin protein expression, reduce vimentin protein expression, inhibit cell invasion and migration in vitro , and inhibit angiogenesis of tumor and decrease plasma VEGF level in nude mouse. In tumor tissues of HCC patients, IL-17 protein expression was negatively correlated with E-cadherin protein expression (r  = –0.622, P  < 0.001), positively correlated with Vimentin protein expression (r  = 0.540, P  < 0.001), and was positively correlated with MVD of HCC tumor tissues (r  = 0.564, P  < 0.001). Compared with adjuvant TACE alone, patients with low-expression of IL-17 treated combined with apatinib have a higher 5-year overall survival. However, additional apatinib treatment did not significantly improve 5-year overall survival in HCC patients with high IL-17 expression. CONCLUSION: IL-17 had a pivotal role in the invasion and angiogenesis of HCC and contribute to the selection of patients who may benefit from adjuvant TACE combined with apatinib. Show more

Keywords: IL-17, transcatheter arterial chemoembolization, hepatocellular carcinoma, overall survival

DOI: 10.3233/CH-200857

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190801

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190735

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

Authors: Brettner, Florian | Heitzer, Markus | Thiele, Friederike | Hulde, Nikolai | Nussbaum, Claudia | Achatz, Stefan | Jacob, Matthias | Becker, Bernhard F. | Conzen, Peter | Kilger, Erich | Chappell, Daniel

Article Type: Research Article

Abstract: BACKGROUND: Hypotension and bradycardia are known side effects of general anesthesia, while little is known about further macro- and microhemodynamic changes during induction. Intriguing is furthermore, why some patients require no vasopressor medication to uphold mean arterial pressure, while others need vasopressor support. OBJECTIVE: Determination of macro- and microhemodynamic changes during induction of general anesthesia. METHODS: We enrolled 150 female adults scheduled for gynaecological surgery into this prospective observational, single-blinded trial. Besides routinely measuring heart rate (HR) and mean arterial blood pressure (MAP), the non-invasive technique of thoracic electrical bioimpedance was applied to measure cardiac output …(CO), cardiac index (CI), stroke volume (SV), stroke volume variability (SVV) and index of myocardial contractility (ICON) before induction of anesthesia, 7 times during induction, and, finally, after surgery in the recovery room. Changes in microcirculation were assessed using sidestream dark field imaging to establish the perfused boundary region (PBR), a validated gauge of glycocalyx health. Comparisons were made with Friedman’s or Wilcoxon test for paired data, and with Mann-Whitney-U test for unpaired data, with post-hoc corrections for multiple measurements by the Holm-Bonferroni method. RESULTS: 83 patients did not need vasopressor support, whereas 67 patients required therapy (norepinephrine, atropine or cafedrine/theodrenaline) to elevate MAP values to ≥70mmHg during induction, 54 of these receiving norepinephrine (NE) alone. Pre-interventional (basal) values of CO, CI, ICON, SV and SVV were all significantly lower in the group of patients later requiring NE (p  < 0.04), whereas HR and MAP were identical for both groups. HR, MAP and CO decreased from baseline to 12 min after induction of general anesthesia in both the patients without and those with NE support. Heart rate decreased significantly by about 25% in both groups (–19 to –21 bpm). The median individual decrease of MAP amounted to –26.7% (19.7/33.3, p  < 0.001) and –26.1% (11.6/33.2, p  < 0.001), respectively, whereas for CO it was –40.7% (34.1/50.1, p  < 0.001) and –43.5% (34.8/48.7). While these relative changes did not differ between the two groups, in absolute values there were significantly greater decreases in CO, CI, SV and ICON in the group requiring NE. Noteably, NE did not restore ICON or the other cardiac parameters to levels approaching those of the group without NE. PBR was measured in a total of 84 patients compiled from both groups, there being no intergroup differences.It increased 6.4% (p  < 0.001) from pre-induction to the end of the operation, indicative of damage to microvascular glycocalyx. CONCLUSION: Non-invasive determination of CO provides additional hemodynamic information during anesthesia, showing that induction results in a significant decrease not only of MAP but also of CO and other cardiac factors at all timepoints compared to baseline values. The decrease of CO was greater than that of MAP and, in contrast to MAP, did not respond to NE. There was also no sign of a positive inotropic effect of NE in this situation. Support of MAP by NE must consequently result from an increase in peripheral arterial resistance, posing a risk for oxygen supply to tissue. In addition, general anesthesia and the operative stimulus lead to an impairment of the microcirculation. Show more

Keywords: Blood pressure, cardiac output, general anesthesia, heart rate, microcirculation

DOI: 10.3233/CH-190691

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2019