Clinical Hemorheology and Microcirculation - Volume 76, issue 2

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 vector flow (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, three of them 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, CCDS (color-coded duplex sonography), V-flow

DOI: 10.3233/CH-209205

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 211-219, 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. 76, no. 2, pp. 221-231, 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. 76, no. 2, pp. 233-240, 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. 76, no. 2, pp. 241-261, 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. 76, no. 2, pp. 263-277, 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. 76, no. 2, pp. 279-285, 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. 76, no. 2, pp. 287-297, 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. 76, no. 2, pp. 299-308, 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. 76, no. 2, pp. 309-316, 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. 76, no. 2, pp. 317-327, 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. 76, no. 2, pp. 329-340, 2020