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

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

Article Type: Research Article

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

Keywords: Ischemia, microcirculation, hemorheology

DOI: 10.3233/CH-170277

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-170298

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

Authors: Negrão de Figueiredo, G. | Mueller-Peltzer, K. | Vincent, S. | Zhang, L. | Rübenthaler, J. | Clevert, D.A.

Article Type: Research Article

Abstract: BACKGROUND: Conventional ultrasound and MRI are very important techniques for the detection of gallbladder alterations. In the past years, studies showed that the additional use of contrast media to the conventional ultrasound allows the early depiction of pathological microvessels and their flow elucidating suspect findings stipulating the prompt therapy approach. OBJECTIVE: The study aims to evaluate the performance of CEUS in gallbladder diseases and compare it to MR imaging using histopathological findings as a gold standard. MATERIAL AND METHODS: The retrospective mono-center study analysed 18 patients with gallbladder alterations between 2009 and 2017. All patients underwent …CEUS and MRI examinations and all results were confirmed in the pathology. CEUS images were performed and interpreted by a single experienced physician. RESULTS: CEUS imaging results compared to MR imaging of the gallbladder demonstrated a sensitivity of 100%, specificity of 93%, a positive predictive value of 67% and a negative predictive value of 100%. CONCLUSION: CEUS enables the depiction and characterization of important vascularization’s patterns facilitating the early differentiation between malignant and benign findings. In this study, CEUS displayed a better diagnostic accuracy than MRI proving to be a valuable additional tool to the established imaging modalities. Show more

Keywords: CEUS, gallbladder alterations, MRI, histopathological findings, adenocarcinoma

DOI: 10.3233/CH-199202

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

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

Article Type: Research Article

Abstract: BACKGROUND: Frequently focal splenic lesions (FSL) - cysts, hemangioma, hamartoma, metastases or infarction amongst others – are incidentally found within the scope of the sonographic examination of the abdomen. By using native B-mode and Color Doppler the underlying entity often is not elucidated. Thus, more elaborate imaging modalities like CT and MRI scans with their associated risks are used to clarify the entity of FSL. PURPOSE: The aim of the present retrospective single-center study is to evaluate the diagnostic performance of CEUS examination for assessing splenic focal lesions by comparison with findings from CT and MRI scans. …MATERIALS AND METHODS: Between 2010–2018 46 patients were included in the study. 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). CEUS examinations were performed and interpreted by a single experienced radiologist (EFSUMB Level 3). RESULTS: All patients were examined without occurrence of any side effects. In total, 53 FSL were investigated (9% traumatic vs. 91 non-traumatic). Compared to CT, CEUS showed a sensitivity, specificity, PPV, NPV of 100% for assessing infarction, hematoma, hamartoma, cystic and malignant lesions. In comparison with MRI, CEUS presented a sensitivity, specificity, PPV, NPV of 100% for evaluating pseudolesions, hemangioma, hamartoma, cystic and malignant lesions. CONCLUSION: With an excellent safety profile CEUS shows an equipollent diagnostic performance for differentiating FSLs compared to CT and MRI scans. Show more

Keywords: Spleen, tumor, focal splenic lesion, contrast-enhanced ultrasound, CEUS

DOI: 10.3233/CH-199204

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

Authors: Tung, Wing Tai | Wang, Weiwei | Liu, Yue | Gould, Oliver E. C. | Kratz, Karl | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: The mechanical properties of electrospun fiber meshes typically are measured by tensile testing at the macro-scale without precisely addressing the spatial scale of living cells and their submicron architecture. Atomic force microscopy (AFM) enables the examination of the nano- and micro-mechanical properties of the fibers with potential to correlate the structural mechanical properties across length scales with composition and functional behavior. In this study, a polyesteretherurethane (PEEU) polymer containing poly(p -dioxanone) (PPDO) and poly(ɛ -caprolactone) (PCL) segments was electrospun into fiber meshes or suspended single fibers. We employed AFM three point bending testing and AFM force mapping to measure the …elastic modulus and stiffness of individual micro/nanofiber and fiber mesh. The local stiffness of fiber mesh including the randomized, intersecting structure was also examined for each individual fiber. Force mapping results with a set point of 50nN demonstrated the dependence of the elasticity of a single fiber on the fiber mesh architecture. The non-homogeneous stiffness along the same fiber was attributed to the intersecting structure of the supporting mesh morphology. The same fiber measured at a point with and without axial fiber support showed a remarkable difference in stiffness, ranging from 0.2 to 10 nN/nm respectively. For the region, where supporting fibers densely intersected, the stiffness was found to be considerably higher. In the region where the degrees of freedom of the fibers was not restricted, allowing greater displacement, the stiffness were observed to be lower. This study elucidates the relationship between architecture and the mechanical properties of a micro/nanofiber mesh. By providing a greater understanding of the role of spatial arrangement and organization on the surface mechanical properties of such materials, we hope to provide insight into the design of microenvironments capable of regulating cell functionality. Show more

Keywords: Biomaterials, AFM, electrospinning, elastic modulus, force mapping

DOI: 10.3233/CH-199201

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Chaloupka, M. | Bischoff, R. | Pfitzinger, P. | Lellig, E. | Ledderose, S. | Buchner, A. | Schlenker, B. | Stief, C. | Clevert, D.-A. | Apfelbeck, M.

Article Type: Research Article

Abstract: INTRODUCTION: Multiparametric (mp) MRI-Ultrasound fusioned biopsy (Fbx) has emerged as the new standard of risk stratification for prostate cancer with superior detection rates of clinically significant prostate cancer (PCa) than randomized biopsy. In this study, we aimed to further investigate clinical cases of detection of insignificant Gleason 6 PCa in patients with suspicion of clinically significant PCa on mpMRI. MATERIAL AND METHODS: Between 2015 and 2019 a total of 234 patients with suspicion of clinically significant cancer on mpMRI were diagnosed with Gleason 6 after Fbx and additional 12-core randomized template biopsy. Patients were retrospectively analyzed for PSA, …clinicopathological results of Fbx, mpMRI results and whole-mount specimen of subsequent prostatectomy. RESULTS: Men with evidence of Gleason 6 in mpMRI-target had a significantly higher amount of positive biopsies (median 4 vs. 2, p  <  0.001) and higher maximum infiltration per biopsy core (30% vs. 20%, p  <  0.001). Detection of Gleason 6 in mpMRI Target lesions correlated significantly with PI-RADS scoring (p  <  0.001). Patients with positive mpMRI-target had significantly higher tumor infiltration in whole-mount specimen after prostatectomy (20% vs. 15%, p  = 0.0026). After prostatectomy, upgrading to significant PCa occured in 57.6% of patients. No significant difference was found between mpMRI-positive or negative patients. In uni- and multivariate analysis no clinical parameter amongst PSA, PI-RADS Score or amount of positive biopsies was identified as a risk factor for upgrading to significant PCa. CONCLUSION: Although Fbx is able to significantly detect Gleason 6 PCa in mpMRI target lesions, upgrading to clinically significant PCa remains unchanged. Show more

Keywords: Low-risk prostate cancer, multiparametric MRI, fusion biopsy, active surveillance, PI-RADS classification

DOI: 10.3233/CH-199223

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

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

Article Type: Research Article

DOI: 10.3233/CH-199217

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Grambow, Eberhard | Dau, Michael | Sandkühler, Niels Arne | Leuchter, Matthias | Holmer, Amadeus | Klar, Ernst | Weinrich, Malte

Article Type: Research Article

Abstract: BACKGROUND: Objective, reliable and easy screening for peripheral artery disease (PAD) is essential to confirm the diagnosis and initiate the respective treatment. Therefore, a new non-invasive hyperspectral camera (TIVITA ® Tissue) was tested in patients with and without PAD. OBJECTIVE: It was hypothesized that the oxygenation parameters of the TIVITA ® Tissue correlate to established modalities for detection of PAD and allow differentiation between individuals with and without PAD. METHODS: Evaluation of tissue oxygenation was performed in the angiosome of the medial plantar artery in 25 healthy young people and in 24 patients with and 25 …patients without PAD in comparable age. Thereby, superficial oxygenation (StO2 ) and near-infrared (NIR) perfusion index were measured with the TIVITA ® Tissue. Additionally, the ankle-brachial-index (ABI), the complaint free walking distance and the vascular quality of life were assessed and demographic data were obtained from all participants. RESULTS: TIVITA ® Tissue analysis revealed significantly reduced StO2 and NIR perfusion index in PAD compared to healthy young participants and patients without PAD. StO2 and NIR perfusion index positively correlated with ABI, the complaint free walking distance and the vascular quality of life score. CONCLUSIONS: In summary, this new hyperspectral imaging camera bears great potential for PAD screening as well as for follow up. Show more

Keywords: Hyperspectral imaging, vascular surgery, screening, perfusion imaging, skin microcirculation

DOI: 10.3233/CH-199215

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2019

Authors: Park, J.W. | Matschke, K. | Mrowietz, C. | Krüger-Genge, A. | Jung, F.

Article Type: Research Article

Abstract: Hyperlipidemic heart transplant patients who develop cardiac allograft vasculopathy (CAV) benefit from HELP-apheresis (H eparin-induced E xtracorporeal L DL P recipitation) which enables drastic lowering of plasma low-density lipoprotein, lipoprotein (a), and fibrinogen. There is evidence that HELP-apheresis also improves microcirculation by an immediate improvement of impaired endothelial-dependent vasodilatation and additive hemorheological effects. Therefore, cutaneous microcirculation was examined before, during, and after the first HELP-apheresis in eight hyperlipidemic cardiac transplant recipients with CAV. To study the long-term effect the intravital microscopy was repeated after three and 12 months of weekly apheresis treatment. In CAV patients the baseline mean …erythrocyte velocity was pathologically reduced with 0.13±0.07 mm/s. During the first HELP-apheresis the erythrocyte velocity increased significantly (p  = 0.0001) and remained increased until the end of the HELP procedure (p  <  0.05). After three months of weekly apheresis treatment a decrease of temporary flow stops in the capillaries with a progressive homogenization (concordance) of the cutaneous microcirculation was observed. After one year of weekly treatment a markedly increase in mean erythrocyte velocity under resting conditions occurred. In addition, a reactive post-ischemic hyperemia could be established for the first time. Even the first single HELP-apheresis resulted in a significant improvement of the cutaneous microcirculation. The long-term treatment of these patients resulted in a marked improvement of the cutaneous microcirculation with the tendency to a normalization of the regulation of the capillary perfusion. Show more

DOI: 10.3233/CH-199216

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Rennert, Janine | Wiesinger, Isabel | Beyer, Lukas Philipp | Schicho, Andreas | Stroszczynski, Christian | Wiggermann, Philipp | Jung, Ernst Michael

Article Type: Research Article

Abstract: AIM: Evaluation of the post-interventional success following ablative techniques (radiofrequency and microwave) using a new color coded perfusion quantification software with CEUS in patients with primary and secondary liver malignancies. MATERIAL AND METHODS: 75 patients (60 males, 15 females, age 24–84 years, mean 62.7 years) with 128 malignant liver lesions were included in this study. Between 01/2013 and 06/2018, the therapeutic interventional procedure in 88 lesions was MWA, in 40 lesions RFA. All patients underwent CEUS using a convex multifrequency probe (1–6 MHz) following application of 1–2,4 ml sulphur hexaflouride microbubbles, before and within 24 hours following RFA and MWA …to detect residual tumor tissue. Postprocessing of the stored DICOM loops from 15 sec up to 1 min using a perfusion quantification software regarding peak enhancement (pE), time to peak (TTP), mean transit time (MTT), rise time (Ri) and Wash-in area under the curve (WiAUC) in the center of the lesion, the border area and periphery was performed. RESULTS: In patients treated with RFA, pE differences between center of the lesion vs. surrounding liver were found to be statistically extremely significant (p  <  0.001), differences between center of the lesion and margin were also statistically significant (p  <  0.01). mTT, TTP, WiAuC and Ri showed no significant difference between center, margin or surrounding liver. In patients treated with MWA, statistically significant differences (p  <  0.05) were found for pE, Ri and mTT regarding the differences between center of lesion and surrounding. WiAuC and TTP showed no significant differences between center, margin or surrounding liver. CONCLUSION: CEUS with perfusion imaging is a valuable supporting tool for post-interventional success control following RFA and MWA of primary and secondary liver maligancies. Focus should be placed upon pE following MWA and pE, Ri and mTT following RFA. Show more

Keywords: Microwave ablation (MWA), radiofrequency ablation (RFA), contrast enhanced ultrasound (CEUS), perfusion analysis, primary and secondary liver malignancies

DOI: 10.3233/CH-199224

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Nies, A. | Proft, L. | Nehring, M.E. | Gruber, C. | Sievers, H. | Hünigen, H. | Rodruigues, A.G. | Gemeinhardt, O. | Mrowietz, C. | Jung, F. | Hiebl, B.

Article Type: Research Article

Abstract: BACKGROUND: In cardiovascular research small pigs breeds like Göttingen ® Minipigs (GM) are established animal models, but systematic data about the micromorphology of the GM vasculature at different ages are scarce. OBJECTIVE: The study was aimed at gaining knowledge about the micromorphology of the femoral artery (FA) from German Landrace pigs (DL) and GM during the period of growth over a body weight range of 10–40 kg. METHODS: FA samples from DL aged two or three months were compared to GM ones, aged 18 or 40 months using transmitted light microscopy. RESULTS: All FA samples …showed typical characteristics of muscular arteries. Growth was associated with increased vessel wall thickness. In the GM this resulted in a slight decrease of the luminal diameter (LD), while in the DL pigs, an increase of the LD and smooth muscle cell content (10%) with decreased elastic fiber content (10%) has been detected. In contrast, within the 22 months lasting growth period of the GM, the tunica media content of smooth muscle cells and elastic fibers remained stable. CONCLUSIONS: FA maturation strongly depends on the pig breed and can be different from what is described in humans. Show more

Keywords: Maturation, micromorphology, muscular artery type, porcine femoral artery, tunica media, Bernhard Hiebl https://orcid.org/0000-0002-6450-0675

DOI: 10.3233/CH-199219

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

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

Article Type: Research Article

Abstract: Laminin-5 (Ln-5), an important ECM protein, plays a critical role in regulating the growth and differentiation of mesodermal tissues, including bone. Ln-5 can be secreted by the mesenchymal stem cells (MSCs), and Ln-5 promotes MSCs osteogenic differentiation. It has been demonstrated that substrate surface topography could regulate MSC secretion and differentiation. A better understanding of the mechanism of Ln-5 and surface roughness regulating MSC osteogenic differentiation, which would provide a guide way for the surface topography design and coating of orthopedic implants and cell culture substrates. However, few studies have investigated the relationship between surface roughness and the secretion of …Ln-5 in the MSC osteogenic differentiation. Whether substrate surface topography regulates MSC differentiation via regulating Ln-5 secretion and how surface topography contributes to the secretion of Ln-5 are still not known. In this study, the influence of microscale roughness at different levels (R0, R1 and R2) on the secretion of Ln-5 of human bone marrow MSCs (hBMSCs) and subsequent osteogenic differentiation were examined. hBMSCs spreading, distribution and morphology were largely affected by different roughness levels. A significantly higher level of Ln-5 secretion was detected on R2, which correlated to the local cell density regulated by the rough surface. Ln-5 binding integrins (α 2 and α 3) were strongly activated on R2. In addition, the results from hBMSCs on R0 inserts with different cell densities further confirmed that local cell density regulated Ln-5 secretion and cell surface integrin activation. And the mineralization level of MSCs on R2 was remarkably higher than that on R0 and R1. These results suggested that hBMSC osteogenic differentiation level on R2 roughness was enhanced via increased Ln-5 secretion that was attributed to rough surface regulated local cell density. Thus, the microroughness could serve as effective topographical stimulus in cell culture devices and bone implant materials. Show more

Keywords: Mesenchymal stem cells, roughness, cell density, laminin-5, osteogenesis

DOI: 10.3233/CH-199205

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Neuber, Christin | Schulze, Sabine | Förster, Yvonne | Hofheinz, Frank | Wodke, Johanna | Möller, Stephanie | Schnabelrauch, Matthias | Hintze, Vera | Scharnweber, Dieter | Rammelt, Stefan | Pietzsch, Jens

Article Type: Research Article

Abstract: Biomaterials coated with artificial extracellular matrices (aECM) are intended to support the healing of critical size bone defects. This pilot study investigated (i) the feasibility of dual tracer PET/CT imaging for functional characterization of biomaterial-assisted bone healing in a rat femoral defect model and (ii) the bone healing ability of polycaprolactone-co -lactide (PCL) scaffolds, coated with various aECM consisting of collagen type I (Col) and glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) or polysulfated hyaluronan (sHA3). [18 F]FDG and [18 F]fluoride PET 4 and 8 weeks after implantation of aECM-coated PCL scaffolds, which provide an in vivo measure of …cellular activation and bone mineralization, respectively, combined with CT imaging (in vivo/ex vivo ) and histologic/immunohistochemical investigations (ex vivo ) showed that coating with CS in particular is beneficial for bone healing. The possible involvement of COX-2 and TGase 2, key enzymes of inflammation and ECM remodeling, in these processes offers starting points for targeted adjuvant therapy in the course of various bone healing phases. Our investigations show the feasibility of the selected dual tracer approach for PET/CT imaging. In principle, this approach can be extended by further PET tracers for the functional characterization of physiological processes such as hypoxia/reperfusion or selected molecular players. Show more

Keywords: Artificial extracellular matrices, bone healing, [18F]fluorodeoxyglucose, [18F]fluoride, glycosaminoglycans, inflammation, metabolism, molecular imaging, revascularization

DOI: 10.3233/CH-199208

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2019

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

Article Type: Research Article

Abstract: INTRODUCTION: Focal therapy (FT) of the prostate for low risk prostate cancer (PCa) is an alternative to traditional definite treatment options like external beam radiotherapy or radical prostatectomy. However, follow up after FT is still challenging and is subject to current studies. Significance of imaging after FT such as multiparametric MRI (mpMRI) is currently not well established. In this study, we aimed to evaluate the efficacy of alternative imaging during the follow up of low risk PCa treated with focal HIFU therapy using CEUS and image fusion. MATERIALS AND METHODS: Retrospective single arm study in patients with uni- …or bilateral, low or intermediate risk prostate cancer treated with HIFU at our institution between October 2016 and January 2018. CEUS in combination with image fusion using an axial T2-weighted MRI sequence was performed during follow up 3, 6, 9 and 12 months after the therapy. RESULTS: 4 consecutive patients with Gleason score (GS) 6 and 4 patients with GS 7a prostate cancer were included in the study. Hemiablation was performed in 7 patients with unilateral tumor. One patient underwent whole gland treatment due to histological proven bilateral PCa. Mean patient age at time of therapy was 70.3 (54–83) years and mean Prostate-specific antigen (PSA) level prior treatment was 7.8 ng/ml (2.1–14.4), after 3 months mean PSA level was 3.9 ng/ml (0.1–7.2), after 6 months 3.5 ng/ml (0.2–6.0), after 9 months 3.1 ng/ml (0.2–6.8) and 3.3 ng/ml (0.2–6.1) after 12 months. CEUS showed no signs of microvascularisation after 3, 6, 9 and 12 months in the ablated zone. 3 months posttreatment the necrotic tissue was still visible in the B-mode scan, although with no signs of vascularization performing CEUS. After 6 months the ablated side of the prostate was almost completely atrophic. And after 9 months the necrotic tissue was completely resolved. Between 9 and 12 months no changes in microvascularisation and perfusion could be shown. CONCLUSIONS: MpMRI/CEUS image fusion is a cost-effective and feasible technique to monitor the perfusion of the ablation zone after focal therapy of the prostate. Show more

Keywords: Prostate cancer, high intensity focused ultrasound therapy, contrast enhanced ultrasound, image fusion, follow up

DOI: 10.3233/CH-199222

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Wiggermann, P. | Krüger-Genge, A. | Jung, F.

Article Type: Editorial

DOI: 10.3233/CH-199200

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

Authors: Monteleone, Adrian | Schary, Weronika | Fath, Andreas | Wenzel, Folker

Article Type: Research Article

Abstract: Although microplastics are commonly defined as very small particles under 5 mm in diameter, they pose an increasingly greater challenge for the environment and all the organisms in it. Particularly, the intake of microplastics into organisms and their impacts and effects on the organism’s functions and metabolism offer a wide variety of research topics. Especially, the effects on mammals and in particular humans have to be investigated. For further investigation of mammalian tissues and fluids, we present an extraction method for microplastic particles out of human blood. After the extraction, which contains a sequence of chemical digestion steps and filtration …over a membrane, the plastic particles are ready for further analysis via FTIR spectroscopy and light microscopy. Show more

DOI: 10.3233/CH-199209

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2019

Authors: Haileka, V. | George, S. | Steinbrecht, S. | Jung, F. | Reinehr, R. | Küpper, J.-H.

Article Type: Research Article

Abstract: BACKGROUND: In most clinical studies older people are underrepresented compared to the demographic reality. However, risk for some severe diseases like cancer typically increase with age. Most insight into cancer treatment comes from mixed-age patient cohorts, leading to a lack of detailed understanding of cancer drug effects in the elderly population. There is growing evidence that cancer drug effects can be influenced by dehydration conditions often found in older people. Colon cancer remains the second leading cause of death by cancer in Europe. Inter- and intra-heterogeneity of tumors contribute to why some individuals do not respond to specific cancer therapies …or may often suffer a relapse. OBJECTIVE: Our study applies an in vitro drug test system for simulating treatment with cytostatics of colorectal cancer in elderly patients with dehydration condition. METHODS: Two well-known colon cancer cell lines, Caco-2 and RKO, harboring defined cancer-related mutations, were step-wisely adapted from routine culture medium to a severe hyperosmotic condition (397 mOmol/kg) by adding sodium chloride to the medium. We investigated the effects of these cell culture conditions, which should mimic cellular dehydration in elderly people, on the growth characteristics of the cells. Therefore, cell proliferation was investigated by measuring population doubling times. Furthermore, we investigated how the metabolic activity of the cells was influenced by treatment with different concentrations of cyclophosphamide (CPA) under normal and hyperosmotic conditions. RESULTS: We found that Caco-2 and RKO cell lines have an identical cell doubling time of 23 hours in normosmotic medium. However, hyperosmotic medium lifted the doubling time of Caco-2 cells to 31 hours while that of RKO cells did not change. Despite reduced cell proliferation rates, hyperosmotic medium sensitized Caco-2 cells to treatment with 10 mM CPA for 48 hours as measured by metabolic activity assays on ATP levels. CONCLUSIONS: The two investigated colon cancer cells lines reacted differently to hyperosmotic conditions. Only the growth of Caco-2 cells was reduced by increased osmolality. Despite this reduced growth their sensitivity to an alkylating cytostatic agent was even slightly increased. We are now in line to examine these effects in more detail and with more tumor cell lines. Show more

Keywords: Colon cancer, cyclophosphamide, dehydration, hyperosmotic, osmolality

DOI: 10.3233/CH-199210

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Brebant, V. | Heine, N. | Lamby, P. | Prantl, L. | Aung, T.

Article Type: Research Article

Abstract: BACKGROUND: A physiological and minimal invasive form of surgery with minimal risk to treat lymphedemas is the so-called supermicrosurgical lymphovenous anastomosis (LVA) where a lymph vessel is connected with a venole. METHODS: Augmented reality intraoperative indocyanin green (ICG) lymphography-navigated modified “simplified lymphovenous anastomosis” were performed on 32 patients (between 2018 and 2019) with secondary upper extremity lymphedema refractory to conservative therapy (manual lymph drainage and compression therapy). For the assessment of lymphatic supermicrosurgery, an operating microscope in which a near-infrared illumination system is integrated (Leica M530 OHX with glow technology ULT530, Leica Microsystems) was used. RESULTS: …63 LVAs were performed with modified “simplified lymphovenous anastomosis” lymphography-guidance on 27 upper extremities and 5 lower extremities. Patency after lymphovenous anastomosis was confirmed by augmented ICG intraoperative microscopy - all patients showed good patency. CONCLUSIONS: Supermicrosurgery in the case of LVA is minimally invasive, highly effective and shows very low complication rate. The practice of LVA is restricted by the surgeon/equipment-related factors, and its effectiveness limited by technical constraints. Show more

Keywords: Lymphedema, lymph node transplantation, lymph vessel transplantation, LVA, augmented reality, indocyanine green (ICG)

DOI: 10.3233/CH-199220

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Reinders, Yvonne | Pohl, Fabian | Ahrens, Norbert | Prantl, Lukas | Kühlmann, Britta | Haubner, Frank

Article Type: Research Article

Abstract: BACKGROUND: To overcome the compromised wound healing in radiation induced chronic wounds platelet-rich plasma (PRP), as therapeutic agent, is current subject of studies. PRP is associated with pro-angiogenic effects. Nevertheless, effects of platelet-rich plasma in cutaneous wound healing processes are poorly understood so far. Methods: In this study, the migration of endothelial cells, fibroblasts and keratinocytes in conjunction with platelet-rich plasma treatment is investigated in the context of radiation effects. Additionally, cell proliferation and viability after external radiation was analyzed regarding treatment by platelet-rich plasma. RESULTS: All cell cultures showed a trend towards decreasing proliferation and …viability after irradiation irrespective of PRP. Upon PRP treatment, irradiated fibroblasts as well as endothelial cells showed an enhanced proliferation whereas proliferation and viability of keratinocytes was reduced after PRP treatment. Scratch assays support the positive effect of PRP on fibroblast and endothelial cell migration, whereas a negative effect on keratinocytes was observed after PRP treatment. CONCLUSIONS: The present study documents both deleterious effects of external radiation as well as the protective effect of PRP. In summary, increased viability, proliferation and migration are indeed a consequence of the pro-proliferative effect exerted by PRP. Therefore, treatment with PRP products might be useful in the management of chronic radiogenic wounds. Show more

DOI: 10.3233/CH-199218

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Schaible, J. | Stroszczynski, C. | Beyer, L.P. | Jung, E.M.

Article Type: Research Article

Abstract: OBJECTIVE: The use of a standardized dynamic contrast enhanced ultrasound (CEUS) protocol to determine perfusion of hepatocellular carcinomas (HCC) using quantitative analysis. METHODS: Retrospective analysis of 27 patients with hepatocellular carcinoma examined by a standardized protocol (bolus injection of 2.4 ml sulphur hexafluoride microbubbles, arterial phase to portal venous phase using continuous CINE-loops over 1 minute, short CINE-loops after 2, 3, 4, 5 and 6 minutes and additional single images for B-mode, CCDS, elastography). The examination was performed by an experienced sonographer with a high resolution, multi-frequency transducer (1–6 MHz). The reading of the reference imaging (contrast enhanced CT and …MRI) and histopathology, if necessary, was performed independently. Retrospective analysis of the CEUS DICOM loops was done using time intensity curves analysis (TIC) with evaluation of the time to peak (TTP) and the area under the curve (AUC). RESULTS: All tumor lesions were characterized by CEUS, based on typical contrast patterns for HCC lesions with arterial enhancement and wash out in the late phase, corresponding to MRI with liver specific contrast agent or contrast enhanced CT. Mean TTP (SD) in the tumor centre (C) was 19.93 (11.31), in the periphery (P) 22.94 (9.44) and in the normal liver tissue (LT) 28.19 (11.34) with significant differences between all zones C/P (p  = 0.013), C/LT (p  = 0.0051) and P/LT (p  = 0.022). AUC mean (SD) in the tumor centre (C) was 660.03 (292.64), in the periphery (P) 586.04 (237.01) and in the normal liver tissue (LT) 484.20 (236.99), also with significant differences between all zones C/P (p  = 0.001), C/LT (p  <  0.001) and P/LT (p  <  0.001). CONCLUSION: TIC-analysis is an easy-to-use tool for the dynamic evaluation of microvascularization in hepatocellular carcinoma and allows a fast and cost-efficient quantitative analysis. Show more

Keywords: CEUS, Contrast enhanced ultrasound, hepatocellular carcinoma, TIC-analysis, quantitative analysis

DOI: 10.3233/CH-199221

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Sun, Xianlei | Tung, Wingtai | Wang, Weiwei | Xu, Xun | Zou, Jie | Gould, Oliver E. C. | Kratz, Karl | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: Electrospinning has attracted significant attention as a method to produce cell culture substrates whose fibrous structure mimics the native extracellular matrix (ECM). In this study, the influence of E-modulus of fibrous substrates on the lineage commitment of human adipose-derived stem cells (hADSCs) was studied using fiber meshes prepared via the electrospinning of a polyetheresterurethane (PEEU) consisting of poly(ρ -dioxanone) (PPDO) and poly(ɛ -caprolactone) (PCL) segments. The PPDO: PCL weight ratio was varied from 40:60 to 70:30 to adjust the physiochemical properties of the PEEU fibers. The cells attached on stiffer PEEU70 (PPDO:PCL,= 70:30) fiber meshes displayed an elongated morphology compared to …those cultured on softer fibers. The nuclear aspect ratio (width vs. length of a nucleus) of hADSCs cultured on softer PEEU40 (PPDO:PCL = 40:60) fibers was lower than on stiffer fibers. The osteogenic differentiation of hADSCs was enhanced by culturing on stiffer fibers. Compared to PEEU40, a 73% increase of osteocalcin expression and a 34% enhancement of alkaline phosphatase (ALP) activity were observed in cells on PEEU70. These results demonstrated that the differentiation commitment of stem cells could be regulated via tailoring the mechanical properties of electrospun fibers. Show more

Keywords: Electrospun fibers, polyetheresterurethane, E-modulus, mesenchymal stem cells, osteogenic differentiation

DOI: 10.3233/CH-199206

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Schiltz, Daniel | Taeger, Christian D. | Biermann, Niklas | Ranieri, Marco | Klein, Silvan | Prantl, Lukas | Geis, Sebastian

Article Type: Research Article

Abstract: BACKGROUND: Reconstruction of soft tissue defects with free flaps is a common procedure in plastic and reconstructive surgery. Most postoperative complications occur within the first 48–72 hours after surgery. After postoperative complications, short perfusion restoration times may improve flap survival rates by up to 30–50%. Ratiometric fluorescence imaging is an additional or alternative method of postoperative flap monitoring. OBJECTIVE: To test the efficacy and utility of transepidermal oxygen flux imaging to evaluate postoperative skin oxygenation of free and local flaps in the first 48 hours after surgery. METHODS: The study included 32 patients (aged between 18 …and 80 years; mean age 52.9) with a tissue defect covered with a free flap transplant at the Department of Plastic and Reconstructive Surgery of the University Medical Center Regensburg. Postoperative oxygen flux was measured with the ‘VisiSens system’ placed on the vascular pedicle as well as on the peripheral and central part of the flap. RESULTS: Values of oxygen flux were higher in case of flap congestion (0.069±0.012) or flap necrosis (0.155±0.083) than in cases without any complications (0.061±0.006). Flux values of different areas of the same flap showed only minimal differences (central part: 0.065±0.008, peripheral part: 0.070±0.009, vascular pedicle: 0.056±0.004); the level of significance was p  = 0.904. CONCLUSION: Imaging transepidermal oxygen flux by ratiometric luminescence seems to be a reliable alternative, indirect method of postoperative flap monitoring with regard to microcirculatory function and flap viability. Show more

Keywords: Postoperative free flap monitoring, microcirculatory function, tissue oxygenation, tissue perfusion, flux imaging, flap monitoring, transcutaneous oxygen measurement

DOI: 10.3233/CH-199225

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Schulz, Christian | Kammerer, Sarah | Küpper, Jan-Heiner

Article Type: Research Article

Abstract: BACKGROUND: Human hepatocyte in vitro cell culture systems are important models for drug development and toxicology studies in the context of liver xenobiotic metabolism. Often, such culture systems are used to elucidate the biotransformation of xenobiotics or drugs and further investigate drug and drug metabolite effects on biological systems in terms of potential therapeutic benefit or toxicity. Human hepatocytes currently used for such in vitro studies are mostly primary cells or cell lines derived from liver cancers. Both approaches have limitations such as low proliferation capacity and progressive dedifferentiation found in primary cells or lack of liver functions …in cell lines, which makes it difficult to reliably predict biotransformation of xenobiotics in patients. In order to overcome these limitations, HepaFH3 cells and Upcyte® hepatocytes representing primary-like hepatocytes of the first and second generation are increasingly used. Based on primary human hepatocyte cells transduced for stable expression of Upcyte® proliferation genes, they are mitotically active and exhibit liver functions over an extended period, making them comparable to primary human hepatocytes. These hepatocyte models show active liver metabolism such as urea and glycogen formation as well as biotransformation of xenobiotics. The latter is based on the expression, activity and inducibility of cytochrome P450 enzymes (CYP) as essential phase I reaction components. However, for further characterisation in terms of performance and existing limitations, additional studies are needed to elucidate the mechanisms involved in phase I reactions. One prerequisite is sufficient activity of microsomal NADPH-cytochrome P450 reductase (POR) functionally connected as electron donor to those CYP enzymes. OBJECTIVE: For Upcyte® hepatocytes and HepaFH3 cells, it is so far unknown to what extent POR is expressed, active, and may exert CYP-modulating effects. Here we studied POR expression and corresponding enzyme activity in human hepatoblastoma cell line HepG2 and compared this with HepaFH3 and Upcyte® hepatocytes representing proliferating primary-like hepatocytes. METHODS: POR expression of those hepatocyte models was determined at mRNA and protein level using qRT-PCR, Western Blot and immunofluorescence staining. Kinetic studies on POR activity in isolated microsomes were performed by a colorimetric method. RESULTS: The investigated hepatocyte models showed remarkable differences at the level of POR expression. Compared to primary-like hepatocytes, POR expression of HepG2 cells was 4-fold higher at mRNA and 2-fold higher at protein level. However, this higher expression did not correlate with corresponding enzyme activity levels in isolated microsomes, which were comparable between all cell systems tested. A tendency of higher POR activity in HepG2 cells compared to HepaFH3 (p  = 0.0829) might be present. Compared to primary human hepatocyte microsomes, POR activity was considerably lower in all hepatocyte models. CONCLUSION: In summary, our study revealed that POR expression and activity were clearly detectable in all in vitro hepatocyte models with the highest POR expression in cancer cell line HepG2. However, POR activity was lower in tested hepatocyte models when compared to human primary hepatocyte microsomes. Whether this was caused by e.g. polymorphisms or metabolic differences of investigated hepatocyte models will be target for future studies. Show more

Keywords: Biotransformation, CYP, cytochrome P450 monooxygenase, HepaFH3, HepG2, hepatocytes, NADPH-cytochrome P450 reductase, POR, Upcyte® hepatocytes, xenobiotics

DOI: 10.3233/CH-199226

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Klingelhoefer, Eric | Hesse, Karl | Taeger, Christian D. | Prantl, Lukas | Stepniewski, Adam | Felmerer, Gunther

Article Type: Research Article

DOI: 10.3233/CH-199213

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Ullrich, Helen | Gori, Tommaso

Article Type: Research Article

Abstract: Percutaneous coronary intervention is the most often used method for coronary revascularization. Stenting restores blood perfusion to ischemic areas, but it also causes mechanical disruption of the atheromatous plaque and the nearby endothelium, stimulating the activation of platelets. In a similar way, platelets are activated by thrombin exposure in the setting of plaque rupture. The interaction between platelets, oxidative stress and inflammation is an important factor determining the extent and severity of vascular dysfunction observed in these settings. Platelets activated by the vessel trauma release inflammatory and mitogenic mediators into the vascular microenvironment, activating leukocyte chemotaxis and switching the endothelial …phenotypefrom a quiescent to an activate one. The increased bioavailability of reactive oxygen species from the vessel wall, from leukocytes and from platelets, and the subsequent decreased bioavailability of nitric oxide, further stimulates platelets, which are otherwise inhibited by this endothelial mediator. Thus, inflammation, oxidative stress and platelet activation cooperate in a feed-forward mechanism leading to vascular dysfunction and possibly compromising the effect of stenting. Inhibitors of platelet function have thus important ancillary effects beyond their antithrombotic ones, which will be discussed in the present short review. Show more

Keywords: Endothelium, thrombosis, acute coronary syndromes, stent

DOI: 10.3233/CH-199214

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2019

Authors: Asam, Claudia | Buerger, Korbinian | Felthaus, Oliver | Rachel, Reinhard | Prantl, Lukas | Witzgall, Ralph | Aung, Thiha | Haerteis, Silke

Article Type: Research Article

Abstract: BACKGROUND: Doxorubicin is a cytostatic drug from the group of anthracycline antibiotics that is widely used as a chemotherapeutic agent. Side effects of the active substance include cardiotoxicity and nephrotoxicity. Doxorubicin-treated renal epithelial cells and (sarcoma) tumors are examined by correlative light and electron microscopy (CLEM) to investigate the subcellular localization of doxorubicin. METHODS: The kidney epithelial cell line MDCK II (Madin-Darby Canine Kidney) grown on culture dishes were treated with doxorubicin. Subsequently, the cells are analyzed by means of fluorescence and transmission electron microscopy (TEM). In vivo , alveolar rhabdomyosarcoma (RH 30) tumor cells are transferred to …the chorioallantoic membrane (CAM) of the chicken embryo. Doxorubicin is injected into a vein of the chicken embryo. After 24 hours, the tumor is removed and examined using CLEM. RESULTS: The kidney epithelial cells and the doxorubicin-injected tumors show a clear staining of the cell nucleus, which correlates with electron-dense regions (heterochromatin). High-resolution TEM shows that doxorubicin treatment leads to an enormous stress situation with an increased formation of membrane blebbings. CONCLUSIONS: CLEM is a promising new method to visualize the pattern of fluorescing drugs (e.g. doxorubicin) in renal epithelial cells and tumors, and to localize the drug in its subcellular context combined with high resolution. Show more

Keywords: Correlative light and electron microscopy (CLEM), chorioallantoic membrane (CAM), doxorubicin, chemotherapy, tumor, sarcoma, Epon

DOI: 10.3233/CH-199212

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Goetz, J. | Kaisermayer, E. | Haase, H. | Jünger, M. | Riebe, H.

Article Type: Research Article

Abstract: BACKGROUND: Although the efficacy of compression therapy through knee-length compression stockings with an interface pressure of 18–21 mmHg for leg oedemas has been confirmed by many studies, 91% of patients are still treated with a higher interface pressure. METHOD: In this prospective open randomised monocentric study 19 patients (age ≥65, movement restrictions and symptomatic leg oedema) received knee-length compression stockings with an interface pressure of 18–21 mmHg (stocking type 1 ) and 23–32 mmHg (stocking type 2 ). On two consecutive days each of the two compression stocking types were worn for at least 8 hours. After this test period, both …stocking types were assessed subjectively and skin changes were recorded. RESULT: A significantly (p -value <0.001) subjective improvement of the symptoms and complaints based on leg oedema was reported with the knee-length compression stockings. The Stocking type 1 recorded a significantly (p  = 0,045) better wearing comfort. In addition, the Stocking type 2 was significantly too large amongst women in the front foot area (p  = 0.044). The most common side effects were constrictions on the proximal lower leg (stocking type 1 = 73,7% (14/19); stocking type 2 = 78,9% (15/19)). Subjects with arthritis (p  = 0.006), hallux valgus (p  = 0.034) and/or digitus flexus (p  = 0.021) found the socking type 1 significantly more comfortable. CONCLUSION: In order to achieve optimal patient compliance it is recommended to prescribe knee-length compression stockings with an interface pressure of 18–21 mmHg if the following criteria are met: age ≥65 years, female sex, arthritis, digitus flexus (claw toe) or hallux valgus. Show more

Keywords: Chronic leg oedema, compression stocking therapy, chronic venous insufficiency, quality of life, wearing comfort

DOI: 10.3233/CH-199207

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Koch, Christoph | Taeger, Christian | Geis, Sebastian | Lonic, Daniel | Heidekrueger, Paul | Dolderer, Juergen | Bitzinger, Diane | Hirche, Christoph | Prantl, Lukas | Kehrer, Andreas

Article Type: Research Article

Abstract: BACKGROUND: Purpura fulminans (PF) is a distinct form of rare meningococcal septicaemia mostly in childhood which is characterized by high lethality, extensive necroses and mutilations of extremities. Other ethiologies are idiopathic forms or purpura neonatorum, which is marked by deficiency of Protein-C. PF is caused by micro-embolism of the vascular system, followed by quickly spreading necroses of skin and different organs. Modern concepts of intensive care treatment of the acute phase of this disease and early surgical intervention lead to a rising number of surviving patients requiring limb salvage. Aim of this study is to evaluate a possible lower morbidity …and the grade of lower loss of function because of early surgical intervention. PATIENTS AND METHODS: Between the years 1998 and 2017 cases of PF at two large centers for critical wound care, the department of plastic-, hand- and reconstructive surgery of the university hospital of Regensburg and the department of plastic-, hand- and reconstructive surgery of the BG-clinic Ludwigshafen patients were included into our study. We retrospectively examined patients with PF who were stabilized by intensive care medicine and received surgical interventions. After survival of the acute phase (10 days), patients received plastic surgical reconstructions. RESULTS: A total number of eight patients could be included into our study. All patients survived the initial phase (10 days). All patients required plastic-surgical interventions to address extensive skin and soft tissue defects. Flap operations were judged necessary in five cases. Hereby four defects could be reconstructed by free tissue transfer, one with a local flap. Flap survival was 100 percent. One flap required revision of the arterial anastomosis of the flap arteria. Another flap got partial necrosis. One patient died due to multiorgan failure. Early debridements with consequent fasciotomies and secondary plastic-surgical reconstruction achieved good functional results. Limb salvage was accomplished in three patients. One patient died due to fulminant progress of the disease. CONCLUSION: Management of PF requires a multidisciplinary approach and close communication between the different subspecialties. Early debridements with consequent fasciotomies showed good results in salvaging subfascial muscle tissue in the extremities with satisfying functional results. Early surgical intervention is an important factor for improved limb salvage and survival. Show more

Keywords: Purpura fulminans, symptoms, surgical management, intensive care management, Idiopathic Thrombocytopenic Purpura, Disseminated Intravascular Coagulation, Acquired Protein C Deficiency, Sepsis, Neisseria meningitidis, Menigococcal sepsis, streptococcus pyogenes, herpes simplex virus

DOI: 10.3233/CH-190588

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Yi, Dong | Benhua, Xu | Qiong, Cao | Qi, Zhang | Yijie, Qiu | Daohui, Yang | Lingyun, Yu | Wen-Ping, Wang

Article Type: Research Article

Abstract: AIM: To investigate the value of contrast enhanced ultrasound with high resolution linear transducers (HF-CEUS) for differential diagnosis of focal fundal gallbladder (GB) wall thickening. METHODS: A total of 32 patients with incidentally detected focal fundal GB wall thickening were included. After conventional B mode ultrasound (BMUS) examinations, HF-CEUS were performed with a 7.5–12 MHz 9L4 linear transducer (S2000 HELX OXANA unit, Siemens). Two radiologists independently reviewed the HF-CEUS enhancement patterns to determine the differential features between malignancy and benignity with a five-point confidence scale. The diagnostic accuracy of BMUS and HF-CEUS for GB wall thickening was compared. The …final gold standard was surgery with histological examination. RESULTS: Final diagnoses included GB adenocarcinoma (n  = 16), adenomyomatosis (n  = 12), Xanthogranulomatous (n  = 2) and cholecystitis (n  = 2). HF-CEUS features associated with GB adenocarcinoma including arterial phase inhomogeneous hyperenhancement, venous phase hypoenhancement and disruption of GB wall layer structure (P  <  0.05). Two small (5 mm) liver metastasis were confirmed by HF-CEUS during the late phase liver sweep as hypoenhanced lesions. Nonenhanced Rokitansky-Aschoff sinuses were clearly observed in 83.3% focal adenomyomatosis. Overall sensitivity, specificity and accuracy for differentiation between malignant and benign focal fundal GB wall thickening of HF-CEUS and BMUS were 84.3% vs 53.1%, 90.6% vs 59.3% and 87.5% vs 56.2% (P  <  0.005). CONCLUSIONS: CEUS performed with high frequency linear transducers could be a useful alternative in the differential diagnosis of focal fundal GB wall thickening on conventional ultrasound. Show more

Keywords: Gallbladder, contrast enhanced ultrasound (CEUS), linear transducer, differential diagnosis, focal wall thickening

DOI: 10.3233/CH-190697

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Wang, S. | Li, B. | Yin, T. | Hong, J. | Gu, J. | Wei, L.

Article Type: Research Article

Abstract: BACKGROUND: The aneurysmal subarachnoid hemorrhage (aSAH) is an acute severe hemorrhagic stroke with high morbidity and mortality with poor prognosis. OBJECTIVE: This study aims to analyze the changes of cerebral venous circulation in patients with aneurysmal subarachnoid hemorrhage by digital subtraction angiography (DSA). MATERIALS AND METHODS: Totally, 57 patients with aSAH, 48 patients with unruptured aneurysms, and 45 patients without aneurysms (control group) were enrolled. The microvascular cerebral circulation time (mCCT), venous cerebral circulation time (vCCT), cerebral arterioles and cortical veins were analyzed by DSA. RESULTS: There were changes of cerebral microvessels and cortical …veins in patients with aSAH. The mCCT (6.15±1.37 s) and vCCT (2.79±0.34 s) of aSAH patients significantly increased compared with control patients (3.74±0.50 s; 2.64±0.32 s) (P  <  0.05). However, the mCCT increased more compared with vCCT in aSAH patients (P  <  0.001), while the vCCT increased more compared with mCCT in severe aSAH cases (P  <  0.01). There was no significant difference in mCCT and vCCT between patients with unruptured aneurysms and controls (P  = 0.131; P  = 0.621). CONCLUSIONS: The mCCT increases in acute aSAH patients within 72 hours and vCCT increases in severe aSAH cases. Show more

Keywords: Aneurysmal subarachnoid hemorrhage, cerebral vein, digital subtraction angiography, microvascular cerebral circulation time, venous cerebral circulation time

DOI: 10.3233/CH-190573

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Chayer, Boris | Allard, Louise | Qin, Zhao | Garcia-Duitama, Julian | Roger, Laurence | Destrempes, François | Cailhier, Jean-François | Denault, André | Cloutier, Guy

Article Type: Research Article

Abstract: BACKGROUND: An enhanced inflammatory response is a trigger to the production of blood macromolecules involved in abnormally high levels of erythrocyte aggregation. OBJECTIVE: This study aimed at demonstrating for the first time the clinical feasibility of a non-invasive ultrasound-based erythrocyte aggregation quantitative measurement method for potential application in critical care medicine. METHODS: Erythrocyte aggregation was evaluated using modeling of the backscatter coefficient with the Structure Factor Size and Attenuation Estimator (SFSAE). SFSAE spectral parameters W (packing factor) and D (mean aggregate diameter) were measured within the antebrachial vein of the forearm and tibial vein …of the leg in 50 healthy participants at natural flow and reduced flow controlled by a pressurized bracelet. Blood samples were also collected to measure erythrocyte aggregation ex vivo with an erythroaggregometer (parameter S 10 ). RESULTS: W and D in vivo measurements were positively correlated with the ex vivo S 10 index for both measurement sites and shear rates (correlations between 0.35–0.81, p  <  0.05). Measurement at low shear rate was found to increase the sensitivity and reliability of this non-invasive measurement method. CONCLUSIONS: We behold that the SFSAE method presents systemic measures of the erythrocyte aggregation level, since results on upper and lower limbs were highly correlated. Show more

Keywords: Erythrocyte aggregation, quantitative ultrasound, shear rate control, human, clinical measurements

DOI: 10.3233/CH-180541

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2019

Authors: Li, Guanhua | Zhang, Yu | Tang, Wei | Zheng, Junmeng

Article Type: Research Article

Abstract: BACKGROUND: Polyamidoamine (PAMAM) dendrimers have been investigated for decades and currently applied in various areas throughout nanomedicine, including gene therapy, drug delivery, anti-bacteria and imaging. It is therefore necessary to assess cytotoxicity of PAMAM dendrimers systematically. Because blood components are usually the initial step of contact with any therapeutic agent, comprehensive hemocompatibility study is needed. MATERIAL S AND METHODS: The triblock dendrimer: polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD), was successfully synthesized. Various in vitro assays to characterize hemocompatibility of both PAMAM (Generation 4.0) and PAMAM-PEG-cRGD were performed, including hemolytic assay, platelet activation examination, platelet counting, assessment of coagulating pathways …and evaluation of complement system activation. RESULTS: The hemolytic ratio of PAMAM-PEG-cRGD maintained below 5%. Surface engineering of PEG and cRGD to PAMAM attenuated hemolysis and RBC aggregation as compared with unmodified PAMAM. PAMAM (Generation 4.0) reduced platelet counting in a dose-dependent manner, and the platelet number dropped dramatically at a relatively low incubating dose (1 μ M). Such surface modifications also alleviated platelet activation and platelet reduction mediated by PAMAM polycationicity. Finally, high concentration (10μ M) of PAMAM interfered the coagulation system, prolonging prothrombin time significantly. CONCLUSION: Surface modification of PEG and cRGD to PAMAM (Generation 4.0) improves hemocompatibility. Introduction of PEG and cRGD significantly mitigates hemolytic and RBC aggregation effects as compared with unmodified PAMAM. Similarly, these modifications alleviate platelet activation and platelet reduction mediated by PAMAM polycationicity. Show more

Keywords: Polyamidoamine (PAMAM), dendrimer, nanoparticle, hemocompatibility, surface modification

DOI: 10.3233/CH-190641

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Wang, Yali | Wu, Feng | Hu, Feng | Wu, Yunjiang | Zhou, Jun | Xu, Yan | Shao, Xiangrong | Hu, Tao

Article Type: Research Article

Abstract: Drag-reducing polymers (DRPs) was previously demonstrated to increase blood flow, tissue perfusion, and reduce vascular resistance. The purpose of this study was to investigate the effect of DRPs on pulmonary vascular remodeling and right ventricular dysfunction in a rat model of chronic hypoxia-induced pulmonary hypertension (HPH). A total of forty male Wistar rats were randomly and equally assigned into four experimental groups (Group I: normoxia + saline, Group II: normoxia + PEO, Group III: hypoxia + saline, Group IV: hypoxia + PEO) and maintained in normoxia (21% O2 ) or hypobaric hypoxia (10% O2 ). After four weeks, comparisons were …made of the following aspects: the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP), right ventricular hypertrophy, wall thickness of pulmonary trunk and arteries, internal diameter of pulmonary arteries, cardiomyocyte cross-sectional area (CM CSA), and ultrastructure of right ventricular. Treatment with PEO in Group IV attenuated the increases in RVSP and mPAP (40.5±7.2 and 34.7±7.0 mmHg, respectively, both P  <  0.05), compared with Group III. Distal vascular remodeling was visible as a significant increase in medial wall thickness (64.2±12.3% vs. 43.95±7.0%, P  <  0.01) and a remarkable decrease in internal diameter of small pulmonary arteries (35.2±9.7μ m vs. 50.4±14.7μ m, P  <  0.01) in Group III, to a greater extent than that detected in Group IV. Nevertheless, no significant histopathological differences in medial wall thickness was observed in pulmonary trunk between Group III and Group IV (P  >  0.05), denoting that PEO chiefly attenuated the remodeling of small pulmonary arteries rather than main arteries in hypoxic environment. Infusion of DRPs (intravenous injection twice weekly) also attenuated the index of right ventricular hypertrophy, protected against the increase of cardiomyocyte cross-sectional area, and provided protection for cardiac ultrastructure. DRP treatment with intravenous injection elicited a protective effect against pulmonary vascular remodeling and right ventricular dysfunction in the rat model of HPH. DRPs may offer a new potential approach for the treatment of HPH, which may have theoretical significance and application value to society. Show more

Keywords: Drag-reducing polymers, vascular remodeling, right ventricular, chronic hypoxia, pulmonary hypertension

DOI: 10.3233/CH-190668

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Raberin, Antoine | Nader, Elie | Ayerbe, Jorge Lopez | Mucci, Patrick | Connes, Philippe | Durand, Fabienne

Article Type: Research Article

Abstract: Blood rheology and hemodynamic parameters have never been explored together during acclimatization to altitude. This study aimed to investigate changes in blood rheology parameters and pulmonary hemodynamics during the first days of real moderate altitude exposure. Seventeen athletes were tested at sea-level, 20 hours after their arrival at 2,400 meters of altitude (H1) and five days later (H2). Blood was sampled to analyze red blood cell (RBC) aggregation, blood viscosity and hematocrit. Pulmonary arterial pressure (PAP), pulmonary capillary pressure (Pcap) and pulmonary vascular resistance (PVR) were assessed by echocardiography. We observed a rise in hematocrit, blood viscosity, RBC …aggregation, PAP, Pcap and PVR between sea-level and H1. In H2, RBC aggregation, hematocrit, PAP, Pcap and PVR remained different compared to SL and no difference was observed between H1 and H2. Blood viscosity decreased in H2 and returned to sea-level values. Our results suggest that hemoconcentration occurring within the first hours of altitude exposure increased blood viscosity, which contributed to the changes in pulmonary hemodynamic. When blood viscosity decreased in H2, no change occurred in pulmonary hemodynamic parameters suggesting that hypoxic pulmonary vasoconstriction was still present. The elevated RBC aggregation observed after in H2 could participate in the increase of Pcap. Show more

Keywords: Moderate altitude, pulmonary arterial pressure, pulmonary vascular resistance, blood viscosity, red blood cell aggregation

DOI: 10.3233/CH-190671

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Xie, Juan

Article Type: Research Article

Abstract: PURPOSE: To evaluate the diagnostic value of quantitative shear wave elastography (SWE) for the differential diagnosis of solid pancreatic tumors. MATERIALS AND METHODS: A total of 66 solid pancreatic masses were enrolled in this study and all the lesions underwent quantitative SWE. The stiffness of the masses was expressed in shear wave velocity (SWV, m/s). The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic performance of quantitative SWE. The optimal cutoff value for SWV in the differentiation of benign from malignant masses was determined. RESULTS: The final diagnoses were 26 benign and 40 …malignant masses. The SWVs were statistically higher for pancreatic malignant masses compared with those for benign masses (3.30±1.22 m/s versus 1.31±0.64 m/s; P  <  0.001). The area under the curve (AUC, 0.93) was obtained. When the best cut-off point was 1.77 m/s, the accuracy, sensitivity, and specificity were 92.4%, 90.0%, and 96.2%, respectively. CONCLUSIONS: Quantitative SWE is a novel technique that can be considered as a quantitative and objective diagnostic tool for prediction of pancreas malignancy. Show more

Keywords: Elasticity imaging techniques, pancreatic neoplasms, ultrasonography

DOI: 10.3233/CH-190665

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Sirufo, Maria Maddalena | Ginaldi, Lia | de Martinis, Massimo

Article Type: Research Article

Abstract: Volleyball players are exposed to the possibility of several well recognized injuries, among which microvascular abnormalities are the less described and studied, although they could diminish their ability and performance. Capillaroscopy is a simple, non-invasive method to diagnose vascular abnormalities in athletes suffering for the consequences of repeated application of pressure by local trauma on the fingertips. The detected capillaroscopic picture will be the base for the follow-up and will indicate the possible need for further investigations aimed at excluding other occulted conditions. At our knowledge, this is the first report describing and documenting the related microvascular abnormalities in a …volleyball player. This case emphasizes the fact that volleyball players among other athletes, whose hands are exposed to repeated fingertips trauma may suffer from microcirculation damage, for which reason they should be able to access an effective health surveillance program able to detect the first signs and offer the most appropriate clinical support. Show more

Keywords: Volleyball, athletes, sport, capillaroscopy, hand, injury, microcirculation, translational medicine

DOI: 10.3233/CH-190667

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-5, 2019

Authors: Lamby, P. | Krüger-Genge, A. | Franke, R.P. | Mrowietz, C. | Falter, J. | Graf, S. | Schellenberg, E.L. | Jung, F. | Prantl, L.

Article Type: Research Article

Abstract: Repeated injections of iodinated contrast media (CM) can lead to a deterioration of the renal blood flow, can redistribute blood from the renal cortex to other parts of the kidney and can cause small decreases of the blood flow in cortical capillaries, a significant reduction in blood flow in peritubular capillaries and a significant reduction in blood flow in the vasa recta. Therefore, a study in pigs was designed, to show whether the repeated injection of CM boli, alone, can cause a reduction of oxygenation in the cortico-medullar renal tissue – the region with the highest oxygen demand in the …kidney - of pigs. While the mean pO2 -value had only decreased by 0.3 mmHg from 29.9±4.3 mmHg to 29.6±4.3 mmHg (p  = 0.8799) after the tenth Iodixanol bolus, it decreased by 5.9 mmHg from 34.0±4.3 mmHg to 28.1±4.3 mmHg after the tenth Iopromide bolus (p  = 0.044). This revealed a remarkable difference in the influence of these CM on the oxygen partial pressure in the kidney. Repeated applications of CM had a significant influence on the renal oxygen partial pressure. In line with earlier studies showing a redistribution of blood from the cortex to other renal areas, this study revealed that Iodixanol – in contrast to Iopromide - induced no changes in the pO2 in the cortico-medullar region which confirms that Iodixanol did not hinder the flow of blood through the renal micro-vessels. These results are in favor of a hypothesis from Brezis that a microcirculatory disorder might be the basis for the development of CI-AKI. Show more

Keywords: Contrast agent, Iodixanol, Iopromide, tissue oxygen partial pressure, CI-AKI, contrast-induced acute kidney injury, ORCID: 0000-0002-9531-2175

DOI: 10.3233/CH-199009

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Vosseler, Markus | El Shazly, Ahmed | Parker, John D | Münzel, Thomas | Gori, Tommaso

Article Type: Research Article

Abstract: BACKGROUND: Evidence of a circadian rhythm in endothelium-dependent vasomotor function, with a nadir in Flow-Mediated Dilation (FMD) in the early morning hours, has been previously reported. These changes have been proposed to be one of the mechanisms explaining the circadian pattern in the incidence of cardiovascular events. We set out to investigate the circadian rhythm of FMD, low-flow mediated dilation (L-FMC) and sympathetic vascular tone. METHODS AND RESULTS: 10 young healthy male volunteers (mean age, 28.9±3.7 years) underwent measurements of radial artery endothelium-dependent FMD and L-FMC at 8AM, 2PM and 8PM on the same day. Sympathetic vascular tone …was assessed with laser Doppler and Fourier transform analysis. Compared with 2PM and 8PM, FMD decreased markedly in the early morning (2.9±3.4%; 6.2±2.9%; 6.0±4.0%; P  = 0.007). In contrast, L-FMC was maximal at 8AM, decreased significantly at 2PM, and returned to higher values at 8PM (–5.1±1.3%; –2.7±2.0%; –4.6±2.2%; P  = 0.030), such that the composite endpoint of endothelial function (sum of FMD+L-FMC) was not significantly different among timepoints. Vascular sympathetic tone was maximal early in the morning and lowest in the evening (P  = 0.014) without a correlation with the changes in FMD or L-FMC. CONCLUSIONS: Endothelial responsiveness (FMD) and basal tone (L-FMC) appear to follow different circadian rhythms, with an impaired responsiveness in the early morning and a nadir in baseline tone in the early afternoon. Show more

Keywords: Endothelial function, circadian rhythm, vascular physiology

DOI: 10.3233/CH-190587

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Ederer, I.A. | Goertz, O. | Bosselmann, T. | Sogorski, A. | Zahn, P.K. | Lehnhardt, M. | Daigeler, A. | Kolbenschlag, J.

Article Type: Research Article

Abstract: BACKGROUND: Mechanism of remote ischemic conditioning (RIC) remain not fully understood yet. Thus, we performed a clinical trial to assess the neuronal influence on its signal induction. METHODS: RIC was conducted on 45 patients who were randomized into 3 groups. Group A and B underwent brachial plexus anesthesia while RIC was performed on the blocked (A) and non-blocked side (B), respectively. In group C, RIC was conducted before regional anesthesia, thus serving as control group. All measurements were taken contralateral to RIC. The relative increase of microcirculatory parameters compared to baseline was evaluated and compared between the groups. …RESULTS: Superficial blood flow (sBF) significantly increased in group A and C but values were higher among group C. Compared to group A, group C showed a significant increase of sBF during the initial 5 minutes of reperfusion (1.75; CI 1.139 – 2.361 vs . 0.97, CI 0.864 – 1.076, p  <  0.05). Deep blood flow, tissue oxygen saturation and relative hemoglobin content were marginally influenced by RIC irrespectively of the presence of regional anesthesia. CONCLUSION: Despite regional anesthesia a significant RIC stimulus can be induced although its microcirculatory response is attenuated compared to control. Hence, RIC induction does not merely depend on neuronal signaling. Show more

Keywords: Remote ischemic conditioning, neuronal signaling, plexus anesthesia, microsurgery, reperfusion

DOI: 10.3233/CH-190626

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190564

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Lin, Lirong | Zhang, Yaxuan | Zeng, Qingxin | Lin, Ligong | Geng, Xiaoli | Wang, Shaobin

Article Type: Research Article

Abstract: OBJECTIVE: To study the atherosclerosis (AS), inflammatory factor level, cognitive disorder and vascular endothelial functions in patients with different grades of leukoaraiosis (LA), and to explore the correlations of different grades of LA with cognitive disorder. METHODS: A total of 180 patients with cerebral infarction admitted and treated in the Department of Neurology of our hospital were selected, and they were graded according to the Tarvonen-shcolder standard, with 45 patients in each group. The atherosclerotic plaques of the patients were detected via a color Doppler ultrasound system and magnetic resonance imaging (MRI). Their inflammatory factor levels were determined …using enzyme-linked immunosorbent assay (ELISA). The cognitive function was scored based on the mini-mental state examination (MMSE), and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), endothelin (ET) and nitric oxide (NO) were measured to evaluate vascular endothelial functions. RESULTS: According to the comparisons among four groups of the patients, the incidence rate of AS was gradually increased among patients with different grades of LA (p  < 0.05). With the aggravation of LA, the levels of inflammatory factors in patients were obviously increased (p  < 0.05). LA patients had evidently lowered MMSE scores and levels of SOD and NO, but notably raised inflammatory factors C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) and vascular endothelial function indices MDA and ET (p  < 0.05). CONCLUSION: The occurrence of LA is implicated with the increasing levels of inflammatory factors in the patients, aggregation of cognitive dysfunction and impairment vascular endothelial functions. Show more

Keywords: Leukoaraiosis, atherosclerosis, inflammatory factors, cognitive function, vascular endothelial functions

DOI: 10.3233/CH-190597

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

Authors: Ugurel, Elif | Connes, Philippe | Yavas, Gokce | Eglenen, Buse | Turkay, Mine | Aksu, Ali Cenk | Renoux, Celine | Joly, Philippe | Gauthier, Alexandra | Hot, Arnaud | Bertrand, Yves | Cannas, Giovanna | Yalcin, Ozlem

Article Type: Research Article

Abstract: BACKGROUND: Erythrocyte deformability is impaired in sickle cell disease (SCD). The regulation of cytoskeletal protein organization plays a key role in erythrocyte deformability. The activation of adenylyl cyclase (AC)/cAMP/Protein kinase A (PKA) signaling pathway was associated with increased deformability in healthy erythrocytes, however the role of this pathway in SCD is unknown. OBJECTIVE: We evaluated mechanical responses of sickle red blood cells under physiological levels of shear stress and the possible link between their deformability and AC/cAMP/PKA signaling pathway. METHODS: The shearing of sickle red blood cells at physiological level (5 Pa) and the measurement of …deformability were performed by a laser assisted optical rotational cell analyzer (LORRCA). RESULTS: Red blood cell deformability increased of 2.5–6.5% by blocking the activity of phosphodiesterase with Pentoxifylline (10μ M) (p  < 0.05). The inhibition of AC with SQ22536 (100μ M) produced more significant rise in deformability (+4.8–12%, p  < 0.01). No significant change was observed by the inhibition of PKA with H89 (10μ M). CONCLUSION: Pentoxifylline and SQ22536 increased the deformability of sickle red blood cells under fluid shear stress. Modulation of the AC/cAMP/PKA pathway could have the potential to be an effective therapeutic approach for SCD through shear-induced improvements of RBC deformability. Show more

Keywords: Protein kinase a, adenylyl cyclase, phosphodiesterase, red blood cell deformability, sickle cell disease

DOI: 10.3233/CH-190563

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Chen, Baoding | Zhang, Zheng | Wang, Keke | Shang, Mengyuan | Zhao, Shuangshuang | Ding, Wenbo | Du, Rui | Yu, Zhuan | Xu, Ximing

Article Type: Research Article

Abstract: OBJECTIVE: To analyze the association of BRAFV600E mutation with ultrasonographic (US) features and clinicopathologic characteristics in Chinese patients with papillary thyroid microcarcinoma (PTMC). METHODS AND MATERIALS: We retrospectively reviewed 116 consecutive Chinese patients with PTMC diagnosed by postoperative pathology. The incidence of the BRAFV600E mutation was calculated. The US features and clinicopathologic characteristics were compared between BRAF-positive and BRAF-negative patients. RESULTS: The BRAFV600E mutation was detected in 60.3% of patients (70 of 116). Multifocality (OR: 3.681, P  = 0.031), non-parallel orientation (OR: 3.181, P  = 0.041) and lymph node metastasis (OR: 4.615, P  = 0.009) were …significantly associated with BRAFV600E mutation. Other US and clinicopathologic characteristics were not significantly related to the presence of BRAF mutation. CONCLUSION: Multifocality, non-parallel orientation and cervical lymph node metastasis are risk factors for BRAFV600E mutation in PTMC. These factors potentially guide treatment planning or prognosis evaluation. Show more

Keywords: BRAFV600E mutation, ultrasonographic features, clinicopathologic characteristics, papillary thyroid microcarcinoma

DOI: 10.3233/CH-190568

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Dong, Yi | Liu, Lingxiao | Cao, Qiong | Zhang, Qi | Qiu, Yijie | Yang, Daohui | Yu, Lingyun | Wang, Wen-Ping

Article Type: Research Article

Abstract: BACKGROUND AND AIM: To evaluate the benefits of contrast-enhanced ultrasound (CEUS) with high frequency transducers in characterization of focal gallbladder lesions (FGL). MATERIAL AND METHODS: From January 2017 to April 2019, 59 FGL detected by B mode ultrasound (BMUS) were examined, first with the low frequency convex transducer (1–5 MHz) and afterwards with high frequency transducer (7.5–12 MHz). High frequency dynamic CEUS were applied after bolus injection of 4.8 ml Sulphur hexafluoride microbubbles (SonoVue® , Milan). The BMUS and CEUS imaging features were recorded and compared. All lesions were confirmed by surgical resection and histopathologic results. RESULTS: The final …diagnoses of 59 FGL included gallbladder adenocarcinoma (n  = 15), gallbladder polyps (n  = 11), gallbladder adenomas (n  = 18), focal adenomyomatosis (n  = 9), and gallbladder Ascariasis debris (n  = 6). The mean diameter of FGL was 24.5±11.4 mm, and mean depth to the abdominal wall was 21.2±7.3 mm. While applying CEUS with high frequency transducer, specific diagnostic features, including arterial phase irregular intralesional vascularity (10/15, 66.7%), late phase hypoenhancement (12/15, 80%), destruction of gallbladder wall (8/15, 53.3%), infiltration to the adjacent liver (6/15, 40.0%) were significantly higher in malignant FGL. The overall sensitivity, specificity and diagnostic accuracy for the correct characterization of malignant FGL were significantly improved by CEUS with high frequency transducer (sensitivity 93.3%, specificity 88.5%, accuracy 100%). CONCLUSION: With its superior contrast resolution, CEUS performed with high frequency transducers is helpful to achieve better visualization of gallbladder fundus and make differential diagnosis of gallbladder lesions, which might greatly improve diagnostic confidence between malignant and benign FGL. Show more

Keywords: Contrast enhanced ultrasound (CEUS), focal gallbladder lesion, high frequency, diagnosis, differentiation

DOI: 10.3233/CH-190639

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Caimi, G. | Raso, S. | Napolitano, M. | Hopps, E. | Presti, R. Lo | Siragusa, S.

Article Type: Research Article

Abstract: Although the inherited quantitative and qualitative disorders of fibrinogen are rare, in the course of time patients may develop complications including episodes of arterial and venous thrombosis. It can be useful to complete the laboratory assessment of these clinical conditions with the evaluation of the haemorheological profile. The data obtained from this study showed that congenital afibrinogenemia was characterized by a primary plasma hypoviscosity, whereas congenital dysfibrinogenemia by a primary plasma hyperviscosity. Both these haemorheological alterations may concur, with different mechanisms, to the pathogenesis of thrombotic vascular complications.

DOI: 10.3233/CH-180542

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Rothe, Rebecca | Schulze, Sabine | Neuber, Christin | Hauser, Sandra | Rammelt, Stefan | Pietzsch, Jens

Article Type: Research Article

Abstract:  The treatment of critical-size bone defects following complicated fractures, infections or tumor resections is a major challenge. The same applies to fractures in patients with impaired bone healing due to systemic inflammatory and metabolic diseases. Despite considerable progress in development and establishment of new surgical techniques, design of bone graft substitutes and imaging techniques, these scenarios still represent unresolved clinical problems. However, development of new active substances gives cause for hope. This work discusses therapeutic approaches that influence angiogenesis or hypoxic situations in healing bone and surrounding tissue. In particular, literature on sphingosine-1-phosphate receptor modulators and nitric oxide (NO• ) …donors, including bi-functional (hybrid) compounds like NO• -releasing cyclooxygenase-2 inhibitors, was critically reviewed with regard to their local and systemic mode of action. Show more

Keywords: Critical-size bone defects, neovascularization, nitric oxide donors, signaling, small molecules, sphingosine-1-phosphate receptor

DOI: 10.3233/CH-199103

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-30, 2019

Authors: Rothe, Rebecca | Schulze, Sabine | Neuber, Christin | Hauser, Sandra | Rammelt, Stefan | Pietzsch, Jens

Article Type: Research Article

Abstract:  Critical-size bone defects after compound fractures, infection, or tumor resection are challenging to treat. The same is true for fractures in patients with impaired bone healing due to metabolic diseases and cancer. Despite considerable progress over the last decade in surgical techniques, material design, and dedicated imaging approaches, these scenarios represent unsolved clinical problems. The high socioeconomic burden of such conditions justifies increasing interest in novel osteoinductive drugs for adjuvant therapeutic approaches. There is an increasing body of experimental and clinical literature on potentially promising effects of growth factors, anti-resorptive, and anabolic agents. The true clinical efficacy of these, however, …is discussed controversially. Therefore, we aimed to critically examine the hypothesis that targeted adjuvant therapies have the potential to enhance bone regeneration in critical-size bone defects and under systemic conditions that impair bone healing. This first approach to the topic deals with small molecule drugs and compounds that influence the immune response and inflammatory processes. In particular, literature reporting on selective cyclooxygenase-2 inhibitors has been reviewed with respect to their local and systemic mode of action and to stimulate further research on bone healing under critical conditions. Show more

Keywords: Biomaterials, critical-size bone defects, cyclooxygenase-2, innate immunity, prostanoids, signaling, small molecules

DOI: 10.3233/CH-199102

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-28, 2019

Authors: Rothe, Rebecca | Schulze, Sabine | Neuber, Christin | Hauser, Sandra | Rammelt, Stefan | Pietzsch, Jens

Article Type: Research Article

Abstract: In this third in a series of reviews on adjuvant drug-assisted bone healing, further possibilities of influencing the healing process are discussed. Local and systemic modulation of bone metabolism is considered during use of a number of drugs with completely different indications, which are characterized by a pleiotropic spectrum of action. These include drugs used to treat lipid disorders (HMG-CoA reductase inhibitors), hypertension (ACE inhibitors), osteoporosis (bisphosphonates), cancer (proteasome inhibitors) and others. Possibilities of their application in the support of bone healing arediscussed.

Keywords: Bisphosphonates, bone metabolism, critical-size bone defects, small molecules, statins, strontium, Wnt signaling

DOI: 10.3233/CH-199104

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-53, 2019

Authors: Jung, Friedrich | Pietzsch, Jens

Article Type: Editorial

DOI: 10.3233/CH-199101

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 2019

Authors: Gilicze, Orsolya | Simon, Diana | Farkas, Nelli | Lantos, Mate | Jancso, Gabor | Berki, Timea | Lenard, Laszlo

Article Type: Research Article

Abstract: BACKGROUND: Composition of pericardial fluid (PF) may reveal immunological processes influencing oxidative stress and microcirculation of different tissues of the heart and may play a role in the course of myocardial infarction, atherosclerosis, and aortic stenosis. PATIENTS AND METHODS: We investigated lymphocyte populations, cardiovascular markers and immunoglobulin composition in PF and blood samples of patients undergoing CABG operation and compared them to those who had aortic valve surgery. RESULTS: The amount of CD8 + T, NK, memoT and activated T-cytotoxic cells were elevated in PF compared to blood, but naiveT and activated T-helper cell ratio were lower in …PF. Amount of activated T-helper cells and regulatory T-lymphocytes were elevated in CABG participants in both PF and blood. INKT cells represented the only regulatory lymphocyte population reaching significantly higher concentration in PF than in blood. IL-6 and MCP1 level were elevated in PF compared to blood and MCP1 plasma level was markedly elevated in CABG group. CONCLUSIONS: Our study describes a comprehensive immunological analysis of PF in humans for the first time. We showed that the investigated lymphocyte populations and cardiovascular markers in PF have significantly different distribution compared to blood, and lymphocyte populations show different compartmentization in coronary disease and aortic stenosis. Show more

Keywords: Lymphocyte populations, cardiovascular markers, immunoglobulin, pericardial fluid, ischemic heart disease, calcific aortic stenosis

DOI: 10.3233/CH-190594

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

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

Article Type: Research Article

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

Keywords: Immature platelet, clopidogrel, aggregometry, ischemic stroke

DOI: 10.3233/CH-190580

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Islam, Sufia | Ahmed, Najneen | Rivu, Sanzana Fareen | Khalil, Marjana | Tanjia, Nafisa | Lehmann, Christian

Article Type: Research Article

Abstract: BACKGROUND: Microvascular dysfunction is a main contributor to morbidity and mortality worldwide. Sophisticated technical tools (e.g. miniaturizedhardware, automated software), along with skilled personnelare the prerequisite for quantitative observations of the microvasculature. OBJECTIVE: This review aimed to get anoverviewabout on-goingmicrocirculatory research in developing countries, particularly of the South-East Asia region for the last five years and to project the challenges faced in microcirculation research in developing countries. METHODS: Original research articles originating from 194 countries were searched in PubMed database on the field of microcirculation research for the last five years. RESULTS: Our findings showed …that around 1800 articles have been published from developing countries compared to more than 5000 from developed countries on different aspects of microcirculation. The overall publication per million populations for developing countries was found to be 0.36 where for developed countries it was 3.62. CONCLUSIONS: Initiation and executionof sophisticated research in microcirculation is a demand of the time. Such research, initially, may seem unmanageable in developing countries with limited resourcesand infrastructuresettings. Collaborativescientificprojectsmay aid in establishingnetworks for microvascular research in developing countries. Show more

Keywords: Microcirculation, infrastructure, developed countries, developing countries

DOI: 10.3233/CH-190611

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190579

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190583

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Rohm, Ilonka | Grün, Katja | Müller, Linda Marleen | Bäz, Laura | Förster, Martin | Schrepper, Andrea | Kretzschmar, Daniel | Pistulli, Rudin | Yilmaz, Atilla | Bauer, Reinhard | Jung, Christian | Berndt, Alexander | Schulze, P. Christian | Franz, Marcus

Article Type: Research Article

Abstract: Growing evidence suggests that inflammation is crucially involved in the pathogenesis of pulmonary hypertension (PH) and consecutive right heart failure. The present study analyzed the inflammatory response in lung and right ventricle in a rat model of PH and evaluated the effects of the dual endothelin receptor antagonist (ERA) Macitentan. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in Sprague-Dawley rats (PH, n  = 10) and compared to healthy controls (CON, n  = 10) as well as monocrotalin-induced, macitentan-treated rats (THER, n  = 10). Detection of Dendritic cells (DCs), regulatory T cells (Tregs) and others as well as RT-PCR based inflammatory gene …expression analysis were performed. Circulating DCs and Tregs were quantified by flow cytometry in the rat model and in PH patients (n  = 70) compared to controls (n  = 52). Inflammatory cells were increased in lung and right ventricular tissue, whereas DCs and Tregs were decreased in blood. Expression of 17 genes in the lung and 20 genes in the right ventricle were relevantly (>2.0 fold) regulated in the PH group. These effects were, at least in part, attenuated in response to Macitentan treatment. In humans as well as rats, immune cells showed significant correlations to clinical, echocardiographic, and haemodynamic parameters. PH is accompanied by a distinct inflammatory response in lung and right but not left ventricular tissue attenuated by Macitentan. Correlations of circulating DCs as well as tissue resident immune cells with parameters reflecting right ventricular function raise the idea of both, promising biomarkers and novel treatment strategies. Show more

Keywords: pulmonary hypertension, right heart failure, inflammation, biomarker, dual endothelin receptor antagonist

DOI: 10.3233/CH-180529

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-26, 2019

Authors: Chen, Chao-Tsung | Hsu, Chung-Hua | Liu, Jyh-Rou | Wu, Hung-Bo | Chou, Yi-Sheng | Hsiu, Hsin

Article Type: Research Article

Abstract: This study tested the hypothesis that measuring and analyzing skin-surface blood flow dynamics can be used to noninvasively discriminate the different microcirculatory and physiological function states of breast-cancer patients with chemotherapy between receiving and not receiving Kuan-Sin-Yin (KSY) treatment. The 17 included patients were assigned randomly to 2 comparison groups: Group K (n  = 10) received KSY treatment, while Group NK (n  = 7) did not receive KSY treatment. Beat-to-beat, spectral, and approximate-entropy (ApEn) analyses were applied to the 20-minute laser-Doppler sequences. The self-reported quality of life and cancer-related symptoms of patients were also investigated. In posttests, Group NK had a significantly …larger ApEn ratio than that in Group K, significantly smaller values of laser-Doppler-flowmetry variability indices, and a slightly higher relative energy contribution of the neural-related frequency band compared to those in the pretests. Almost all cancer-related symptoms showed improvements in Group K compared to in Group NK. The present findings indicated that the present analysis can be used to detect the significantly different responses in the laser-Doppler indices between taking and not taking KSY. The KSY effect was also noted to be accompanied with improvement of EORTC QLQ-C30 scores. These could lead to a rapid, inexpensive, and objective technique for enhancing clinical applications in quality-of-life monitoring of breast cancer therapy. Show more

Keywords: Breast cancer, blood flow, laser Doppler, approximate entropy, spectral analysis

DOI: 10.3233/CH-190569

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180489

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2019

Authors: Veres, T.Gy. | Petrovics, L. | Sárvári, K. | Vereczkei, A. | Jancsó, G. | Farkas, K. Borbásné | Takács, I.

Article Type: Research Article

Abstract: INTRODUCTION: Pneumoperitoneum, widely used in laparoscopic surgery increases the intraabdominal pressure, leading to hypoperfusion of the abdominal organs, and promoting the buildup of reactive oxygen species(ROS) and inflammatory cytokines which in turn impairs the body postoperatively. Aim of our investigation was to evaluate the potential protective effects of short ischemic episodes on ischemic damages. METHODS: 70 Wistar rats were used, divided into 7 groups: 1st group sham, 2nd group pneumoperitoneum with 5 mmHg, 3rd group preconditioning with 5 mmHg, 4th group: postconditioning with 5 mmHg, 5th group pneumoperitoneum with 10 mmHg, 6th group: preconditioning with 10 mmHg, 7th group postconditioning with 10 mmHg. Pneumoperitoneum …was created by Veres needle. Oxidative stress parameters: malondialdehyde (MDA) concentration, reduced glutathione (GSH), sulfhydril (SH-), myeloperoxidase (MPO) levels and superoxide-dismutase (SOD) activity were measured. We measured TNF-α and IL-6 concentrations. We monitored the activation of anti- and proapoptotic common signaling pathways (bax, bcl-2, p53) during the early phase of reperfusion. Histology was made from kidney samples. RESULTS: GSH concentrations were significantly reduced, MDA concentrations were significantly higher in each group compared to the Sham. SOD enzyme: a pressure of 10 mmHg elicited significantly greater damage than 5 mmHg. There was a significantly higher SOD activity in group 10 mmHg IPC compared to 10 mmHg. We found that the expression of bax was considerably higher in the none conditioned groups. Noticeably higher expression of anti-apoptotic bcl-2 level was measured in 10 mmHg IPC and 10 mmHg IPoC groups. In case of p53 expression: significant decrease could be seen in groups 10 mmHg IPC and 10 mmHg IPoC compared to the 10 mmHg group. CONCLUSION: Based on our results, the elevated intraabdominal pressure due to pneumoperitoneum induces oxidative stress, which is dependent on the applied pressure. Mostly precondiotioning – but also postconditioning – reduces surgical stress following laparoscopic procedures. In order to explore its mechanism it requires further investigations. Show more

Keywords: Laparoscopy, preconditioning, postconditioning, oxidative stress

DOI: 10.3233/CH-190572

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Biran, Roni | Hadayer, Noa | Ramot, Yuval | Zlotogorski, Abraham | Yedgar, Saul | Barshtein, Gregory

Article Type: Research Article

Abstract: BACKGROUND: Alternations in erythrocyte deformability (ED), namley, the ability of erythrocytes to change shape under flow in the microcirculation, can contribute to cardiovascular diseases. Psoriasis, a systemic inflammatory skin disorder, is associated with an increased cardiovascular risk. The effect of psoriasis and psoriasis treatment on ED was only scarcely evaluated. OBJECTIVE: To evaluate ED changes in psoriasis patients following narrow band-ultraviolet B (NB-UVB) treatment. METHODS: Erythrocyte deformability was determined using a computerized cell flow properties analyzer in 9 patients with psoriasis before and after a course of Goeckerman regimen. ED was quantified using two parameters: average …elongation ratio (AER) in the cell population, and the fraction of low deformable cells (% LDFC). RESULTS: All 9 patients showed decreased ED (i.e. impaired deformability) following NB-UVB treatment. There was a significant (p  = 0.003) decrease in AER after treatment (AER±SD; 1.58±0.06) compared to the starting values (1.69±0.1). Additionally, there was a significant (p  = 0.002) increase in the fraction of low deformable cells (% LDFC±SD; 60.00±9.05) compared to their fraction before treatment (34.86±11.44). CONCLUSIONS: The decreased ED observed following phototherapy could have clinical influences on psoriasis patients, and may partially explain why phototherapy does not decrease the cardiovascular risk in psoriasis compared to other treatments. Show more

Keywords: Psoriasis, phototherapy, erythrocytes, deformability, comorbidities, cardiovascular disease

DOI: 10.3233/CH-180424

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180532

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190559

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Martini, Romeo

Article Type: Research Article

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

DOI: 10.3233/CH-190576

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2019

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180492

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

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

Article Type: Research Article

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

Keywords: Electrocardiography, magnetocardiography, diagnostic performance

DOI: 10.3233/CH-180485

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180432

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

Authors: Liu, Haifang | Zhu, Yuping | Jiao, Jie | Yuan, Jia | Pu, Tianning | Yong, Qiang

Article Type: Research Article

Abstract: The aim of this study was to assess the elasticity of Hashimoto’s thyroiditis in the different processes via supersonic ShearWave™ Elastography (SWE™). Quantitative information is delivered as Young’s modulus value expressed in kilo-Pascal (kPa). 30 healthy female and 30 healthy male individuals aging at 40±20 y had undergone conventional ultrasonography and SWE to determine the influence of gender on elasticity of thyroid. Also 60 female and 60 male patients (mean age, 40±20 y) with Hashimoto’s thyroiditis in different processes underwent conventional ultrasonography and SWE to determine the elasticity of thyroid in Hashimoto’s thyroiditis. Furthermore, the relationship between elasticity values and …thyroid peroxidase antibody (TPOAB) in the patients was investigated. We found significant impact of gender on elasticity values of healthy thyroids. Our study showed that increased elasticity values with statistical significance in hyperthyroidism stage, normal thyroid function stage and hypothyroidism were shown. Low degree relationship between elasticity values and TPOAB was found in 60 male patients. However, there was no such correlation in female patients. Show more

Keywords: ShearWave™ elastography, hashimoto’s thyroiditis, ultrasound imaging, elasticity

DOI: 10.3233/CH-170347

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