Clinical Hemorheology and Microcirculation - Volume 76, issue 4

Authors: Marschner, C.A. | Zhang, L. | Schwarze, V. | Völckers, W. | Froelich, M.F. | von Münchhausen, N. | Schnitzer, M.L. | Geyer, T. | Fabritius, M.P. | Rübenthaler, J. | Clevert, D.-A.

Article Type: Research Article

Abstract: BACKGROUND: HCC as the 6th most common tumor entity with the fourth highest mortality and an increasing prevalence especially due to today’s lifestyle acquires a high attention in the clinical setting. Beside CECT and CEMRI, CEUS depicts a dynamic, low-risk and radiation free imaging method that finds its use mainly in screening and active surveillance programs. PURPOSE: The aim of the retrospective study was to evaluate the diagnostic value of CEUS in correlation to pathologic findings. MATERIALS AND METHODS: Between 2004 and 2018 a total number of 119 patients were included in this retrospective single-center study. …Every patient underwent CEUS in addition to a native B-mode and Color-Doppler scan. After given informed consent SonoVue ® (Bracco, Milan, Italy), a second-generation blood-pool agent, was used as contrast medium. Every examination was performed and interpreted by a single experienced radiologist (EFSUMB level 3). A low mechanical index (MI) of <0,2 was chosen to obtain a good imaging quality. RESULTS: All 119 included patients received CEUS followed by a liver biopsy for inter-modality comparison. In correlation to the pathology results, CEUS showed a diagnostic sensitivity of 96,6%, a specificity of 63,9%, a PPV of 86,7% and a NPV of 88,5% by detecting liver lesions suspicious for HCC. According to the Cohen’s Kappa coefficient (k = 0,659) CEUS shows a strong inter-modality agreement in comparison to the histopathological finding. CONCLUSION: With a high sensitivity and a strong cross-modality comparability to histopathology, the CEUS is highly effective in the detection of suspicious HCC lesions. Show more

Keywords: HCC, liver, CEUS, histopathology

DOI: 10.3233/CH-209221

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 4, pp. 453-458, 2020

Authors: Engel, P. | Ranieri, M. | Felthaus, O. | Geis, S. | Haubner, F. | Aung, T. | Seyfried, T. | Prantl, L. | Pawlik, MT.

Article Type: Research Article

Abstract: BACKGROUND: A key moderator of wound healing is oxygen. Wound healing is a dynamic and carefully orchestrated process involving blood cells, cytokines, parenchymal cells (i.e. fibroblasts and mesenchymal stem cells) and extracellular matrix reorganization. Human adipose derived stem cells as well as human fibroblasts produce soluble factors, exhibit diverse effects on inflammation and anti inflammation response and are involved in wound healing processes. Hyperbaric oxygen therapy is an effective adjunct treatment for ischemic disorders such as chronic infection or chronic wounds. In vitro effects of hyperbaric oxygen therapy on human cells were presented in many studies except for those …on mono- and co-cultures of human adipose derived stem cells and fibroblasts. OBJECTIVE: The aim of this study was to investigate the effects of hyperbaric oxygen therapy on mono- and co-cultures of human adipose derived stem cells and fibroblasts. METHODS: Mono- and co-cultures from human adipose derived stem cells and fibroblasts were established. These cultures were exposed to hyperbaric oxygen therapy every 24 h for five consecutive days. Measuring experiments were performed on the first, third and fifth day. Therapy effects on the expression of VEGF, IL 6 and reactive oxygen species were investigated. RESULTS: After exposure to hyperbaric oxygen, cell culturess showed a significant increase in the expression of VEGF after 3 and 5 days. All cultures showed significantly reduced formation of reactive oxygen species throughout the experiments. The expression of IL-6 decreased during the experiment in mono-cultures of human adipose derived stem cells and co-cultures. In contrast, mono-cultures of human skin fibroblasts showed an overall significantly increased expression of IL-6. CONCLUSIONS: Hyperbaric oxygen therapy leads to immunmodulatory and proangiogenetic effects in a wound-like enviroment of adipose derived stem cells and fibroblasts. Show more

Keywords: HBO therapy, adipose derived stem cells, cell oxygenation, cell co-culture, angiogenesis, hyperbaric oxygen

DOI: 10.3233/CH-209222

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 4, pp. 459-471, 2020

Authors: Monteleone, Adrian | Brandau, Lena | Schary, Weronika | Wenzel, Folker

Article Type: Research Article

Abstract: INTRODUCTION: More and more researchers are studying the effects of microplastics on the environment and the organisms living in it. Existing detection methods still require a heavy workload, complex sample preparation and high costs. In this study, autofluorescence of plastic was used as a new method for microplastic detection. MATERIAL AND METHODS: Particles of common plastics were incubated at various temperatures (21–230 °C) for different time periods to investigate the influence of these conditions on their autofluorescence using methods like fluorescence microscopy, and measurement of absorption and emission. To give an example of an autofluorescence application, ImageJ was …used to determine the contamination of microplastic in sea salt samples. RESULTS: After treatment at 140 °C for 12 h the plastics ABS, PVC and PA showed a distinct increase in their fluorescence intensity. For PET higher temperatures were necessary to achieve higher fluorescence intensities. Using ImageJ, the particle contamination in sea salt samples was determined as 4903±2522 (aluminium membrane) / 5053±2167 (silicone membrane) particles in 10 g salt, which is a much higher number than counted in other publications. DISCUSSION: Probably the increase in fluorescence intensity is due to the movement of atomic bonds caused by the thermic energy during the heat treatment. The high number of counted particles by using ImageJ is most likely based on the smaller pore size of the used filter membranes and other contaminations like dust and fibers, which could be avoided by alternative sample treatment. CONCLUSION: Considering the outcomes of this study, heat treatment is a useful tool to make microplastic particles more visible in microscopic applications without readable destruction of their composition. The heat treatment of plastics for defined incubation times and temperatures can lead to a distinct increase in autofluorescence intensity of the plastics and therefore serve as an easy and cost-effective applicable method for microplastic detection. Show more

DOI: 10.3233/CH-209223

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 4, pp. 473-493, 2020

Authors: Biermann, Niklas | Sommerauer, Laura | Diesch, Sophia | Koch, Christoph | Jung, Friedrich | Kehrer, Andreas | Prantl, Lukas | Taeger, Christian D.

Article Type: Research Article

Abstract: BACKGROUND: The biophysical interaction induced by low energy pulsed electromagnetic field therapy (PEMFT) on the capillary microcirculation is not well understood. Several studies indicate a significant effect of PEMFT in patients with chronic medical conditions. OBJECTIVE: The aim of this study was to evaluate the influence of PEMFT on skin microcirculation in healthy volunteers. METHODS: 15 healthy participants were included. Nine PEMF treatments were applied over three weeks in an 48-hour interval. The PEMFT system (BEMER) was placed beneath one of the participants’ leg with the contralateral side serving as a control. A forty-minute application period …was preceded by a 10-minute resting phase. Measuring was done using two Laser Doppler probes (LEA) placed on each anterior lateral thigh. RESULTS: All outcome parameters including flow, mixed venous oxygen saturation and relative venous hemoglobin showed a significant increase during the experiment when compared to the baseline values of the resting phase in both groups (p  < 0.01). Comparing both groups, the measurement values during the experiment did not differ (p  > 0.05) except for higher flow values in the control group (P  = 0.03). Over time, baseline values of both groups showed no significant difference (p  > 0.05). CONCLUSION: We found a significant increase of all measurement parameters during the study compared to the baseline values with no difference between the PEMF and control group. Show more

Keywords: Pulsed electromagnetic field therapy (PEMFT), microcirculation, cutaneous blood flow

DOI: 10.3233/CH-209224

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 4, pp. 495-501, 2020

Authors: Apfelbeck, Maria | Pfitzinger, Paulo | Bischoff, Robert | Rath, Lukas | Buchner, Alexander | Mumm, Jan-Niklas | Schlenker, Boris | Stief, Christian G. | Chaloupka, Michael | Clevert, Dirk-André

Article Type: Research Article

Abstract: OBJECTIVE: The aim of this study was to evaluate clinical features associated with benign histopathology of Prostate Imaging Reporting and Data System (PI-RADS) category 4 and 5 lesions. MATERIALS AND METHODS: Between March 2015 and November 2020, 1161 patients underwent mpMRI/Ultrasound-fusion-guided prostate biopsy (FBx) and concurrent 12-core systematic prostate biopsy (SBx) at the Department of Urology of the Ludwig-Maximilians-University of Munich, Germany. 848/ 1161 (73%) patients presented with either PI-RADS 4 or 5 index lesion and were retrospectively evaluated. Multivariate analysis was performed to evaluate clinical parameters associated with a negative outcome of PI-RADS 4 or 5 category …lesions after FBx. Area under the receiver operating characteristics (ROC) curve (AUC) was conducted using ROC-analysis. RESULTS: 676/848 (79.7%) patients with either PI-RADS 4 or 5 index lesion were diagnosed with prostate cancer (PCa) by FBx and 172/848 (20.3%) patients had a negative biopsy (including the concurrent systematic prostate biopsy), respectively. Prostate volume (P-Vol) (OR 0.99, 95% CI = 0.98–1.00, p  = 0.038), pre-biopsy-status (OR 0.48, 95% CI = 0.29–0.79, p  = 0.004) and localization of the lesion in the transitional zone (OR 0.28, 95% CI = 0.13–0.60, p  = 0.001) were independent risk factors for a negative outcome of FBx. Age (OR 1.09, 95% CI = 1.05–1.13, p  < 0.001) and PSA density (PSAD) (OR 75.92, 95% CI = 1.03–5584.61, p  = 0.048) increased the risk for PCa diagnosis after FBx. The multivariate logistic regression model combining all clinical characteristics achieved an AUC of 0.802 (95% CI = 0.765–0.835; p  < 0.001) with a sensitivity and specificity of 66% and 85%. CONCLUSION: Lesions with high or highly likelihood of PCa on multiparametric magnetic resonance imaging (mpMRI) but subsequent negative prostate biopsy occur in a small amount of patients. Localization of the lesion in the transitional zone, prostate volume and prebiopsy were shown to be predictors for benign histopathology of category 4 or 5 lesions on mpMRI. Integration of these features into daily clinical routine could be used for risk-stratification of these patients after negative biopsy of PI-RADS 4 or 5 index lesions. Show more

Keywords: Prostate cancer, multiparametric magnetic resonance imaging, PI-RADS lesions with high or very high likelihood of clinically significant prostate cancer, risk stratification, targeted biopsies

DOI: 10.3233/CH-209225

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 4, pp. 503-511, 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. 76, no. 4, pp. 513-523, 2020

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

Keywords: Laser doppler flowmetry, melanoma detection, malignant melanoma, neuronal network, case series

DOI: 10.3233/CH-200876

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 4, pp. 525-533, 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 this pilot study was to evaluate the alterations in RBC eNOS activity and intracellular NO generation in PAH patients 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 lower in RBC from PAH patients. ROCK inhibitor increased basal eNOS activity and improved NO generation capacity of RBC of PAH patients to healthy control levels. PS exposure levels were also higher in RBC of PAH patients. CONCLUSIONS: This study provides first evidences for decreased RBC eNOS activity due to its ROCK mediated negative regulation in PAH patients. Considering increased ROCK activity contribution 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. 76, no. 4, pp. 535-548, 2020

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

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

Keywords: Contrast-enhanced ultrasound, pseudoaneurysm, thrombin

DOI: 10.3233/CH-200923

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 4, pp. 549-557, 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. 76, no. 4, pp. 559-572, 2020