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

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

Article Type: Research Article

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

Keywords: Ischemia, microcirculation, hemorheology

DOI: 10.3233/CH-170277

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-170298

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180429

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

Authors: Jung, Friedrich | Connes, Philippe | Lehmann, Christian

Article Type: Editorial

DOI: 10.3233/CH-199008

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 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: 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: 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: Martínez-Quintana, Efrén | Rodríguez-Hernández, Juan Lizandro | Riaño-Ruiz, Marta | Rodríguez-González, Fayna

Article Type: Research Article

Abstract: BACKGROUND: Platelet activation is linked with thrombosis, inflammation or heart failure. OBJECTIVE: To establish clinical and analytical factors that may favor high mean platelet volume (MPV) and to determine if MPV levels favor major adverse cardiovascular events (MACE). METHODS: Stable CHD patients and a control population matched for age, sex and cardiovascular factors. RESULTS: 658 CHD patients and 2092 controls were studied. Median age in CHD patients was 33 (25–41) year old with 56% of them being male. No significant differences were seen between MPV values and cardiac complexity (p  = 0.308) nor between MPV …values in the CHD and control groups (p  = 0.911). CHD patients had significant lower platelet count and MPV levels than patients in the control group. In the binary logistic regression analysis NT-pro-BNP levels above 125 pg/ml, thrombocytopenia and having atrial fibrillation/flutter reached statistical significance as predictors of MPV levels above 11 fL. The Kaplan-Meier survival analysis showed no significance between MPV levels higher than 11 fL and MACE, cardiovascular mortality and thrombotic events in a median time follow-up of 6.7(1.5–10.6) years. CONCLUSIONS: Atrial fibrillation/flutter, heart failure and thrombocytopenia are predictors of high MPV levels. A MPV above 11 fL is not associated with MACE at a median follow-up time. Show more

Keywords: Mean platelet volume, inflammation, heart failure, congenital heart disease

DOI: 10.3233/CH-180471

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

Authors: Ludolph, Ingo | Cai, Aijia | Arkudas, Andreas | Lang, Werner | Rother, Ulrich | Horch, Raymund E.

Article Type: Research Article

Abstract: BACKGROUND: Free tissue transfer has become a routine procedure with low failure. In case of a compromised vascular pedicle, flap survival is time dependantly possible due to flap autonomization. However it remains unknown at what time and to which degree different factors influence flap autonomization. METHODS: We investigated 16 patients after free flap reconstruction at different anatomic locations who eventually presented for other medical reasons. To assess the perfusion pattern we performed Indocyanine Green angiography. RESULTS: The mean follow-up after free flap reconstruction was 58,1 month. A total of 16 flaps were examined at different anatomic …locations. In 2 cases digital subtraction angiography demonstrated an occlusion of the anastomosis after arteriovenous loop despite vital flaps. Indocyanine Green angiography showed no signs of mal-perfusion or non-perfusion in the transplanted flaps and capillaries across the flap borders in 9 cases. CONCLUSION: Flap autonomization is possible even in patients with problem wounds and poorly vascularized wound beds independent from the anatomic localization. Multiple factors exist, that influence the autonomization process over time. Indocyanine Green angiography seems to be a promising tool to visualize and study the skin perfusion pattern of free flaps over longer periods. Show more

Keywords: Vascular autonomization, free flaps, indocyanine green angiography, microcirculation

DOI: 10.3233/CH-180544

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

Authors: Iamaguchi, Raquel | Burgos, Felipe | Silva, Gustavo | Cho, Alvaro | Nakamoto, Hugo | Takemura, Renan | Wei, Teng | de Rezende, Marcelo | Mattar Jr, Rames

Article Type: Research Article

Abstract: BACKGROUND: The optimal number of veins to be anastomosed in perforator flaps for limb reconstruction and its influence on the results remain controversial. Venous thrombosis of microvascular anastomoses is a commonly recorded complication in soft tissue reconstruction. OBJECTIVE: To evaluate the effect of two venous anastomoses in the incidence of venous thrombosis for limb reconstruction using anterolateral thigh (ALT) microsurgical free flaps. METHODS: This was a cross-sectional study on patients undergoing limb reconstruction using ALT flap during 2014–2017. Perioperative information was recorded and patients were divided in two groups: group 1 (one venous anastomosis; 17 patients) …and group 2 (two venous anastomoses; 21 patients). Complications were investigated. RESULTS: Overall, 38 microsurgical flaps were included. The mean age was 33 years, and 32 patients were male. The most prevalent wounds were traumatic. Group 1 presented a higher complication rate than group 2 (47% vs. 24%; p  = 0.065), although the difference was not significant. Group 1 presented a higher rate of venous anastomotic thrombosis (p  = 0.032) than group 2. The overall success rate was 92%. CONCLUSION: For limb reconstruction using ALT microsurgical free flaps, two venous anastomoses are associated with a low rate of venous thrombosis in microvascular anastomoses. Show more

Keywords: Thrombosis, microcirculation, free tissue flaps, postoperative complication, thigh/surgery

DOI: 10.3233/CH-180467

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 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: Stupin, Ana | Stupin, Marko | Baric, Lidija | Matic, Anita | Kolar, Luka | Drenjancevic, Ines

Article Type: Research Article

Abstract: OBJECTIVE: To assess sex-related differences in forearm skin microvascular reactivity to vascular occlusion and cardiovascular health in young healthy women and men. METHODS: 203 young healthy individuals (67 men/136 women) participated in this study. Post-occlusive reactive hyperemia (PORH) in skin microcirculation following 1′ , 2′ and 3′ vascular occlusion period was assessed using laser Doppler flowmetry. Anthropometric parameters, body composition, blood pressure, heart rate and biochemical parameters were measured in all participants. Correlations between PORH and measured parameters were determined by using corresponding tests. RESULTS: Women had significantly higher forearm PORH following 1′ , …2′ and 3′ vascular occlusion than men. Women had lower body mass index and waist-to-hip ratio, but higher fat mass than men. Men had significantly higher blood pressure and lower heart rate than women. Also, women had lower hemoglobin, urea, creatinine and serum uric acid, but higher HDL cholesterol level than men. PORH was negatively associated with waist-to-hip ratio and systolic blood pressure only in women. CONCLUSIONS: Young healthy women exhibit higher skin microvascular reactivity to vascular occlusion compared to age-matched men. Increased systolic blood pressure or central obesity (waist-to-hip ratio) may pose greater risk to young healthy women than men by adversely affecting peripheral microvascular function. Show more

Keywords: Keywords: Sex differences, microcirculation, endothelium, laser Doppler flowmetry, post-occlusive reactive hyperemia

DOI: 10.3233/CH-180483

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

Authors: Kapnisis, K. | Seidner, H. | Prokopi, M. | Pasias, D. | Pitsillides, C. | Anayiotos, A. | Kaliviotis, E.

Article Type: Research Article

Abstract:  Despite their wide clinical usage, stent functionality may be compromised by complications at the site of implantation, including early/late stent thrombosis and occlusion. Although several studies have described the effect of fluid-structure interaction on local haemodynamics, there is yet limited information on the effect of the stent presence on specific hemorheological parameters. The current work investigates the red blood cell (RBC) mechanical behavior and physiological changes as a result of flow through stented vessels. Blood samples from healthy volunteers were prepared as RBC suspensions in plasma and in phosphate buffer saline at 45% haematocrit. Self-expanding nitinol stents were inserted in …clear perfluoroalkoxy alkane tubing which was connected to a syringe, and integrated in a syringe pump. The samples were tested at flow rates of 17.5, 35 and 70 ml/min, and control tests were performed in non-stented vessels. For each flow rate, the sample viscosity, RBC aggregation and deformability, and RBC lysis were estimated. The results indicate that the presence of a stent in a vessel has an influence on the hemorheological characteristics of blood. The viscosity of all samples increases slightly with the increase of the flow rate and exposure. RBC aggregation and elongation index (EI) decrease as the flow rate and exposure increases. RBC lysis for the extreme cases is evident. The results indicate that the stresses developed in the stent area for the extreme conditions could be sufficiently high to influence the integrity of the RBC membrane. Show more

Keywords: Cardiovascular stent, blood viscosity, red blood cell deformability, red blood cell aggregation, lysis

DOI: 10.3233/CH-180540

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-19, 2019

Authors: Wang, Minxin | Sui, Jingshu | Wang, Shuang | Wang, Xiaoting

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the correlation of carotid intima-media thickness (IMT) with endothelial function and atherosclerosis degree in patients with type 2 diabetes mellitus. METHODS: A total of 80 patients with type 2 diabetes mellitus admitted and treated in our hospital from January 2017 to January 2018 were selected and randomly divided into two groups (n  = 40). Patients who were definitely diagnosed with type 2 diabetes mellitus were selected as observation group, and individuals who received health examination and were excluded from type 2 diabetes mellitus were enrolled as control group. The diagnosed proportions of carotid plaque, Crouse scores, …endothelial-dependent flow-mediated vasodilation (FMD) function and nitroglycerin-mediated dilation (NMD) function of the brachial arteries in the two groups were compared. The indexes related to vascular endothelial functions [vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and nitric oxide (NO) levels] in the two groups were detected. The correlations of Crouse score with brachial arterial FMD value, VEGF level, ET-1 level and NO level in observation group were analyzed. RESULTS: The diagnosed proportion of carotid plaque in observation group was significantly higher than that in control group (P  < 0.05), and the Crouse score in observation group was higher than that in control group (P  < 0.05). The brachial arterial FMD value in observation group was remarkably lower than that in control group (P  < 0.05). Compared with control group, VEGF and ET-1 levels were significantly reduced in observation group (P  < 0.05), with the statistical increase of NO level (P  < 0.05). In observation group, the Crouse score was negatively correlated with the brachial arterial FMD value, VEGF level and ET-1 level, whereas positively correlated with the NO level (P  < 0.05). CONCLUSION: Our data show that the carotid IMT is increased significantly among patients with type 2 diabetes mellitus, and the vascular endothelial function is impaired. Moreover, after the occurrence of atherosclerosis, we found the carotid IMT is negatively correlated with endothelial-dependent FMD, as well as levels of VEGF and ET-1, whereas shows positive correlation with the vasodilative factor NO. Show more

Keywords: Type 2 diabetes mellitus, carotid intima-media thickness, endothelial function, carotid plaque

DOI: 10.3233/CH-180486

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

Authors: Mizeva, I.A | Potapova, Elena V | Dremin, Viktor V | Zherebtsov, Evgeny A | Mezentsev, Mikhail A | Shupletsov, Valerii V | Dunaev, Andrey V

Article Type: Research Article

Abstract: The variation of blood flow characteristics caused by the probe pressure during noninvasive studies is of particular interest within the context of fundamental and applied research. It has been shown previously that the weak local pressure induces vasodilation, whereas the increased pressure is able to stop the blood flow in the compressed area, as well as to significantly change optical signals. The blood flow oscillations measured by laser Doppler flowmetry (LDF) characterize the functional state of the microvascular system and can be used for noninvasive diagnostics of its abnormality. This study was intended to identify the patterns of the …relationship between the oscillating components of blood flow registered by the LDF method under different levels of pressure applied to an optical fiber probe. For this purpose, we have developed an original optical probe capable of regulating the applied pressure. The developed protocol included six sequential records of the blood perfusion at a pressure within the 0 to 200 mmHg range with unloading at the last stage. Using wavelet analyses, we traced the variation of energy of oscillations for these records in five frequency bands associated with different vascular tone regulation mechanisms. Six young volunteers of the same age (three males and three females) were included in this preliminary study and the protocol was repeated five times in each volunteer. Accordingly, 30 LDF records were available for the analyses. As expected, the LDF signal increases at weak pressure (30 mmHg) and decreases at increased pressure. The statistically stable amplification of endothelial associated blood flow oscillations under the 90 mmHg pressure allowed us to put forward a hypothesis that the endothelial activity increases. The possible causes of this phenomenon are discussed. Show more

DOI: 10.3233/CH-180459

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

Authors: Her, Ae-Young | Shin, Eun-Seok | Zhou, Qing | Wierzbinski, Jan | Vidal-Lopez, Silvia | Saleh, Ahmed | Kim, Yong Hoon | Garg, Scot | Jung, Friedrich | Brachmann, Johannes

Article Type: Research Article

Abstract: BACKGROUND: Magnetocardiography (MCG) is a non-invasive technique and to characterize the magnetic field, a pseudo-current conversion was used. The role of MCG in detecting left atrial (LA) dysfunction in patients with paroxysmal atrial fibrillation (PAF) is unknown. OBJECTIVE: The aim of this study was to evaluate LA function using MCG in patients with PAF and healthy subjects, to identify possible indices to diagnose PAF. METHODS: We enrolled a total of 70 subjects including 26 healthy volunteers (group 1) and 22 marathon runners (group 2) who did not exhibit any cardiac abnormalities, and 22 patients with PAF …(group 3) which was documented by electrocardiography (ECG). Spatiotemporal activation graph (STAG) in base-apex and left-right direction was reconstructed. The maximum value of LA pseudo-current under rest and peak exercise were measured between the end of the P wave and beginning of the Q wave. RESULTS: LA pseudo-current increase at peak exercise in PAF patients was significantly lower than in healthy volunteers and marathon runners (0.4±0.3 pT in group 3 vs. 0.8±0.3 pT in group 1 vs. 1.1±0.5 pT in group 2, p  <  0.001). PAF patients had less pseudo-current increase in STAG at peak exercise than healthy and marathon runners (46% of 26 PAF patients, 81% of 22 healthy subjects vs. 81% of 22 marathon runners, p  = 0.002). Sensitivity, specificity, and the area under the receiver-operator characteristics curve of LA pseudo-current increase at peak exercise for differentiating PAF patients from healthy subjects were 77%, 92%, and 0.896. CONCLUSIONS: MCG can provide important non-invasive information for detecting LA dysfunction in PAF patients. Therefore, MCG may help in differentiating PAF patients from healthy subjects. Show more

Keywords: Left atrium, dysfunction, magnetocardiography, paroxysmal atrial fibrillation

DOI: 10.3233/CH-180528

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 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: Muenchow, S. | Horch, R.E. | Dragu, A.

Article Type: Research Article

Abstract: BACKGROUND: Topical negative pressure wound therapy (TNPWT) is one of the most frequently used techniques in wound treatment. But the underlying mechanism remains unclear. One possible explanation is an improved microcirculation by TNPWT. OBJECTIVE: This study investigated the influence of TNPWT on microcirculation on intact skin in real-time. METHODS: In healthy individuals, we performed a combined tissue – laser/photo - spectrometry technique to monitor changes of 4 different microcirculation parameters in real-time: The local blood flow, the capillary-venous oxygen saturation, the blood flow velocity and the relative amount of hemoglobin. We compared these parameters using two …different protocols: a continuously (VAC ON 60/OFF 60) and discontinuously (VAC ON 30/OFF 60/ON 5) application. RESULTS: Our results demonstrate a significant increase of all four measured parameters during the active TNPWT and the pressure free period. The comparison of two different protocols shows an advantage of the examined parameters using a discontinuous TNPWT application. CONCLUSIONS: Our study demonstrated the changes of the microvascular tissue perfusion in intact human skin under the conditions of negative pressure and may thereby offer a broader understanding about the mechanism of the TNPWT. Show more

Keywords: Topical negative pressure wound therapy, tissue – laser/photo – spectrometry, microvascular tissue perfusion

DOI: 10.3233/CH-180536

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

Authors: Fang, Liang | Huang, Bei-jian | Ding, Hong | Mao, Feng | Li, Chao-lun | Zeng, Meng-su | Zhou, Jian-jun | Chen, Yue | Wang, Wen-ping

Article Type: Research Article

Abstract: AIM: To investigate the specific findings and characteristics of real-time contrast-enhanced ultrasound (CEUS) in hypoechoic hepatic hemangioma. METHODS: A total of 101 lesions in 83 patients were included. Analysis was made of the relationship between tumor size and CEUS enhance patterns in arterial phase, portal phase and delayed phase, phase changes, echoic changes in perfusion regression stage and filling defect. RESULTS: CEUS showed a lesion detection rate of 92.7% . In regression stage, only 46.5% lesions were fully filled. Enhancement of the lesions was categorized into Pattern I, peripheral nodular enhancement and centripetal filling (68.3%); Pattern …II, peripheral ring enhancement and centripetal filling (27.7%); and Pattern III, overall rapid enhancement (4.0%). The most common phase changes were “fast-in slow-out” (74.3%). More than half (61.4%) lesions were hyperechoic in regression stage. Among all the lesions, 4 (3.9%) lesions regressed to hypo-echo in portal phase and 2(2.0%) in delayed phase). The frequent enhancement in tumors >3.0 cm was of Pattern I or II, “fast-in slow-out” or “slow-in slow-out” phase change, and hyperechoic or isoechoic change in perfusion regression stage, but in those ≤3.0 cm, the enhancement was of Pattern III, “fast-in fast-out” phase change and hypoechoic change in perfusion regression stage. The differences were statistically significant (p  <  0.05). The percentage of lesions with complete filling on CEUS in the larger hypoechoic hepatic hemangiomas was significantly lower than that of smaller ones (p  <  0.01). CONCLUSIONS: CEUS has high diagnostic value in hypoechoic hepatic hemangiomas mainly characterized by peripheral nodular or ring enhancement, centripetal filling, and “fast-in slow-out” and “slow-in slow-out” phase changes. Show more

Keywords: Hypoechoic hepatic hemangioma, contrast-enhanced ultrasound (CEUS), enhancement pattern

DOI: 10.3233/CH-190558

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

Authors: Gnasso, Agostino | Cacia, Michele | Cutruzzolà, Antonio | Minieri, Marilena | Carallo, Claudio | Cortese, Claudio | Irace, Concetta

Article Type: Research Article

Abstract: BACKGROUND: The relationship between blood viscosity (BV) and endothelial function is rather complex. An increase in BV causes an increase in blood flow resistance, with negative hemodynamic effects; on the other hand, a moderate increase in BV causes an increase in wall stress shear (WSS), and consequent beneficial effects. As a matter of fact, the effect of changes in BV on endothelial function is not yet clear. OBJECTIVES: Aim of the present study was to evaluate in-vivo the effects of the acute reduction in BV on endothelial function, in healthy male subjects. METHODS: Fourteen healthy …male blood donors were studied before and 48 hours after blood donation. Blood and plasma viscosity were measured at 37C° with a cone-plate viscometer. Endothelial function was evaluated through flow mediated vasodilation (FMD). RESULTS: Blood viscosity was reduced after blood donation (BV225 (cP) 4.53±0.59 vs.4.18±0.31, p  <  0.05). FMD 50 s after cuff deflation was unchanged: 6.23±3.84 vs. 6.62±4.81, p  = NS. The vasodilation, however, lasted longer and the area under the curve of FMD was significantly increased: 8.74±8.77 vs.16.14±8.65, p  <  0.005. CONCLUSIONS: The present results demonstrate that the acute reduction of BV prolongs vasodilation, without affecting the amount of vasodilatation, possibly as adaptive reaction allowing more time for oxygen release. Show more

DOI: 10.3233/CH-180446

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 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: Sheremet’ev, Yury A. | Popovicheva, Aleksandra N. | Rogozin, Methun M. | Levin, Grigory Ya.

Article Type: Research Article

Abstract: BACKGROUND: Diabetes mellitus is frequently associated with microcirculation pathology and hemorheological disorders. METHODS: 24 patients with diabetic foot and 22 healthy subjects were recruited. RBC aggregation, disaggregation and morphology of aggregates were determined in autologous plasma and serum. RESULTS: The RBC aggregation in patients with diabetic foot increased in autologous plasma and serum. Increased red blood cell aggregate strength in these patients was observed only in autologous plasma. Microscopic images of RBC aggregates of patients with diabetic foot show the formation of pathologic globular structures of aggregates in autologous plasma and serum. CONCLUSION: The …RBC aggregation in autologous plasma and autologous serum in patients with diabetic foot is significantly higher than in healthy subjects. Increase in strength of RBC aggregates in diabetic foot patients was observed only in autologous plasma. The microscopic images of RBC aggregates in patients with diabetic foot indicate the formation of globular (pathologic) structures of aggregates in autologous plasma and serum. The differences in the morphology of RBC aggregates in autologous plasma and serum between healthy subjects and diabetic foot patients, obtained by microscopic image analysis with high magnification light microscope, can be used as an additional diagnostic tool in medical practice. Show more

Keywords: Diabetic foot, red blood cell aggregation, disaggregation, aggregates morphology, autologous plasma, autologous serum

DOI: 10.3233/CH-180405

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

Authors: Ulker, Pinar | Özen, Nur | Abduleyeva, Günel | Köksoy, Sadi | Yaraş, Nazmi | Basralı, Filiz

Article Type: Research Article

Abstract: BACKGROUND: Rho-kinase, an effector of the small GTPase RhoA, is known to be a novel inhibitory regulator of eNOS in endothelial cells under basal conditions and disease states. However, although RBC possesses active RhoA/Rho-kinase pathway, Rho-kinase mediated eNOS regulation has not been investigated in RBC, so far. OBJECTIVE: The aim of the present study is to investigate whether eNOS activity is regulated by Rho-kinase under basal conditions and to evaluate whether inhibition of this enzyme causes eNOS activation and intracellular NO production in RBC. METHODS: RBC packeds were isolated from healthy volunteers and resuspended in Hepes …solution at a hematocrit of 0.01 l/l. Intracellular NO and Ca +2 levels and eNOS activation measured by flow cytometry in response to Rho-kinase inhibitors, fasudil and Y-27632, in the absence and presence of NOS, and PI3K inhibitors. RESULTS: Rho-kinase inhibitors fasudil and Y-27632 found to increase intracellular NO concentrations. These inhibitors also cause enhancement of intracellular Ca +2 and serine 1177 phosphorylated eNOS levels. Besides, although these responses have shown to be suppressed by NOS enzyme, PI3K inhibition had no effect on this mechanism. CONCLUSIONS: The results of the present study demonstrated that RBC eNOS enzyme activity is regulated by inhibitory Rho-kinase pathway under basal conditions and inhibition of this pathway enhances the activity of eNOS in RBC. This activation is mediated by both intracellular Ca +2 and Serine 1177 phosphorylated eNOS increment, with no contribution of AKT activation, in RBC. The mechanism we described here gives first evidences about Rho-kinase mediated eNOS regulation in RBC under basal conditions. This pathway could also be more important under disease states. Show more

Keywords: Red blood cells, Rho-kinase, nitric oxide, nitric oxide synthase

DOI: 10.3233/CH-190578

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

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

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to evaluate the impact of thyroid nodule sizes on the diagnostic performance of Korean thyroid imaging reporting and data system (TIRADS) and contrast-enhanced ultrasound (CEUS). METHODS: In total, 308 consecutive patients with 382 thyroid nodules underwent US-guided FNA or surgery were included in this retrospective study. The nodule size was classified into 3 categories: ≤10 mm (group A), 10–20 mm (group B), and ≥20 mm (group C). We compared the risk of malignancy in each subgroup, categorized according to the TIRADS and CEUS patterns. RESULTS: In group A, the differences in diagnostic value between TIRADS …and CEUS were significant (AUC: 0.804 vs 0.733, P  = 0.028, sensitivity: 81.8% vs 72.7%, P  = 0.013, specificity: 88.9% vs 79.4%, P  = 0.011). In group B, the AUC (0.897), sensitivity (88.1%) and specificity (91.9%) of CEUS were highest. In group C, the specificity of CEUS was significantly higher compared with TIRADS classification (90.8% vs 82.9%, P  = 0.023), while the sensitivity and AUC showed no significant difference between the two models (84.2% vs 81.5%, P  >  0.406, 0.848 vs 0.820, P  = 0.545). CONCLUSIONS: Nodule size influences the diagnostic accuracy of the two methods. TIRADS have best value in nodules ≤10 mm, while CEUS perform best for differentiating lesions >10 mm, especially in lesions ≥20 mm. Show more

Keywords: Thyroid ultrasound, nodule size, thyroid malignancy, contrast-enhanced ultrasound, TIRADS, Biopsy

DOI: 10.3233/CH-180545

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

Authors: Cao, Jiaying | Dong, Yi | Fan, Peili | Mao, Feng | Wang, Wenping

Article Type: Research Article

Abstract: BACKGROUND: Dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) with quantitative analysis is updated in recent years. OBJECTIVE: To explore the feasibility of dynamic 3D-CEUS in evaluation of dynamic vascular patterns of focal liver lesions (FLL), and to analyze the correlation of time-intensity curve (TIC) parameters between dynamic 3D-CEUS and two-dimensional CEUS (2D-CEUS). METHODS: Dynamic 3D-CEUS and 2D-CEUS were both carried out in 106 FLL cases with SonoVue. Divided into arterial, portal and late phases, dynamic 3D-CEUS image quality of 106 FLLs were scored by 2 readers separately and graded according to the overall score. The 2D-CEUS and identical …3D-CEUS TIC parameters of the same FLL were compared and the correlation of these parameters were analyzed. RESULTS: A satisfactory correlation (0.953) and a good inter-observer agreement (0.700) of 2 readers were achieved by using five-point score scale to image quality in 3 phases of dynamic 3D-CEUS. The boundaries of FLLs were clearest in arterial phase on dynamic 3D-CEUS. The depth and vascularization of FLLs only had influence on its image quality in only arterial phase (P  = 0.002 and 0.000 respectively). The comparison of quantification between dynamic 3D-CEUS and 2D-CEUS of 56 FLLs were also underwent. Interclass correlation coefficient (ICC) of mean transit time (MTT) and time to peak (TP), were both 0.96, and Pearson correlation coefficients of all 5 TIC parameters were no less than 0.90 between dynamic 3D-CEUS and 2D-CEUS. CONCLUSION: Dynamic 3D-CEUS is technically feasible and can be used for clinical evaluation of the perfusion of FLL avoiding adverse factors of sampling. Quantitative 3D-CEUS parameters are stable and reliable, and have good correlation with those of 2D-CEUS. Show more

Keywords: Three-dimensional, contrast-enhanced ultrasound, two-dimensional, focal liver lesion

DOI: 10.3233/CH-180531

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

Authors: Quan, Juan | Hong, Yurong | Zhang, Xu | Mei, Mei | You, Xiangdong | Huang, Pintong

Article Type: Research Article

Abstract: OBJECTIVE: To clarify the clinical role of contrast enhanced ultrasound (CEUS) in predicting BI-RADS 4 breast disease. METHODS: A total of 92 sites of BI-RADS 4 breast diseases were reassessed by routine ultrasound and CEUS. The main indicators of routine ultrasound, CEUS and the combination of the two modalities were picked up by binary logistic regression analysis, scoring 0 for benign and 1 for malignant characteristics with pathology as referential standard to generate corresponding score systems of them. Finally, the receiver operating characteristic curves (ROC) were applied to compare the diagnostic efficacy of the three score systems. …RESULTS: As pathological results showing, there were 43 malignant and 49 benign sites in total. Binary logistic regression analysis indicated that the margin, micro-calcification, and hyperechoic halo were main indicators for routine ultrasound score system. The scope expansion and pathological vessels in CEUS were main indicators for CEUS score system. The microcalcification, hyperechoic halo, the scope expansion and pathological vessels in CEUS were main indicators for the combination score system of the two modalities. The sensitivity, specificity and the area under ROC curve (AUC) of routine US, CEUS and the combination of the two modalities score systems were 74.4%, 91.8%, 0.885 and 88.4%, 87.8%, 0.901 and 86.0%, 95.9%, 0.937, respectively. CONCLUSION: In summary, CEUS is helpful for us to identify malignant disease and plays a supplementary role in predicting BI-RADS 4 breast disease in some extent. The scope expansion and pathological vessels in CEUS may be the most useful indicators. Show more

DOI: 10.3233/CH-180495

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

Authors: Suker, Mustafa | Tovar Doncel, M. Sherezade | Pinto Lima, Alexandre A. | Ince, Can | van Eijck, Casper H.J

Article Type: Research Article

Abstract: Background: An observational cohort study was conducted to identify potential sublingual microcirculation parameters as a target for goal-directed fluid therapy. Methods: Patients that were scheduled for an open elective pancreatico-biliary surgery in Erasmus Medical Center were included. All patients underwent sublingual microcirculatory measurement at three time points: one day before surgery (T0), within the first 24 hours after surgery (T1) and on the fourth day after surgery (T2). The following parameters were obtained: microvascular flow index (MFI (AU)), Total vessels density (TVD (mm/mm2/)), Perfused vessels density (PVD (mm/mm2)), and proportion of perfused vessels (PPV (%)). Results: …Sixteen patients were included in the final analysis. The differences between the time points T1 and T0 in patients without clinical significant complication and in patients with these complications gave a significant difference for PVD small vessels (PVDs) (delta PVDs mean -0.1 vs -8.2, p=0.01) and PPV small vessels (PPVs) (delta PPVs median 7.0 % vs -15.5 %, p=0.01). Conclusion: The most significant microcirculatory parameter for a perioperative complicated course is the change of PVD and PPV. In the first 24 hours after surgery, if these parameters decrease there is a high chance of a complicated perioperative course. Show more

Keywords: Pancreatectomy, microcirculation, morbidity

DOI: 10.3233/CH-180448

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

Authors: Li, Xiang | Hou, Xiu-Juan | Du, Lin-Yao | Wu, Jia-Qi | Wang, Luo | Wang, Hong | Zhou, Xian-Li

Article Type: Research Article

Abstract: OBJECTIVE: This study was conducted to investigate the diagnostic performance of Virtual Touch Tissue Imaging and Quantification (VTIQ), combined with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) in differentiating malignant and benign thyroid nodules. METHODS: A total of 130 thyroid nodules in 128 patients were included. The diagnostic performance of conventional ultrasound (US), VTIQ, and the combination of these two techniques was calculated and compared according to the area under the receiver operating characteristic curve (AUROC), for sensitivity, specificity, and accuracy. RESULTS: The sensitivity and specificity for the ACR TI-RADS …were 98.6% (72/73) and 24.6% (14/57), respectively. There was a strong agreement with ACR TI-RADS categories of thyroid nodules (all ICCs >  0.60). With an optimal cutoff value of 2.46 m/s, the sensitivity and specificity of the minimal shear wave velocity (SWVmin ) were 87.7% (64/73) and 70.2% (40/57). By applying this value to downgrade or upgrade ACR TI-RADS, the specificity significantly increased from 24.6% (14/57) to 47.4% (27/57; P  <  0.05) and the sensitivity remained at 98.6% (72/73). CONCLUSIONS: VTIQ combined with ACR TI-RADS could improve the specificity of the differential diagnosis of thyroid nodules without a loss of sensitivity. Show more

Keywords: Ultrasound, elastography, thyroid nodule, thyroid imaging reporting and data system, virtual touch tissue imaging and quantification

DOI: 10.3233/CH-180477

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

Authors: Li, H. | Ding, X. | Lu, L. | Yang, J. | Ma, J.

Article Type: Research Article

Abstract: PURPOSE: To explore the normal morphological features of the retinal periarteral capillary free zone (paCFZ) and the changes associated with severe non-proliferative diabetic retinopathy (NPDR) by optical coherence tomography angiography (OCTA). METHODS: A total of 148 normal subjects and 115 patients with severe NPDR were enrolled. Spectral-domain OCTA was used to acquire the image with a Cirrus prototype. Diameter and area of each paCFZ quadrant and adjacent large artery diameter was estimated. RESULTS: In healthy subjects, the maximum width of paCFZ in the temporal quadrant (169.38 ± 19.26 μ m) was smaller than the other three quadrants …(all P <0.001). The ratio of maximum paCFZ width to artery caliber was much larger in the nasal quadrants than the rest quadrants (Ps <0.05). In patients with severe NPDR, both maximum width and area of paCFZ were significant larger, and the retinal artery inner diameters significant smaller in each quadrant compared to normal subjects (Ps <0.05). The ratio of paCFZ maximum width to artery caliber maximum width was significant greater, and the ratio of paCFZ area to artery caliber was significantly higher in all quadrants compared to normal eyes (Ps <0.05). CONCLUSIONS: OCTA provides noninvasive and quantitative measurement of paCFZ dimensions. The maximum width and area of paCFZ quadrants and the ratios of these parameters to adjacent inner artery width and area are elevated in severe NPDR, suggesting that changes in paCFZ dimension can be used as clinical indices for diseases associated with changes in retinal microcirculation and oxygen pressure. PRÉCIS: Optical coherence tomography angiography revealed differences in retinal periarteral capillary free zone (paCFZ) morphometry between health retina and severe non-proliferative diabetic retinopathy. Morphometric indices of paCFZ may be useful for monitoring disease occurrence and progression. Show more

Keywords: Non-proliferative diabetic retinopathy; periarteral capillary free zone; optical coherence tomography angiography

DOI: 10.3233/CH-180458

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 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: Filar-Mierzwa, Katarzyna | Marchewka, Anna | Dąbrowski, Zbigniew | Bac, Aneta | Marchewka, Jakub

Article Type: Research Article

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

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

DOI: 10.3233/CH-180470

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180444

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

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

Article Type: Research Article

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

Keywords: Cardiac hypertrophy, MEK inhibitor, TAK733, norepinephrine

DOI: 10.3233/CH-180476

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180484

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180515

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180404

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180450

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

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

Article Type: Research Article

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

DOI: 10.3233/CH-180449

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

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

Article Type: Research Article

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

DOI: 10.3233/CH-189908

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

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

Article Type: Research Article

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

Keywords: Endothelial glycocalyx, neuraxial anesthesia, joint surgery

DOI: 10.3233/CH-180428

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180454

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180434

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180377

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

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

Article Type: Research Article

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

Keywords: Hypernatremia, endothelial glycocalyx, sublingual microcirculation, syndecan

DOI: 10.3233/CH-189907

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

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

Article Type: Research Article

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

DOI: 10.3233/CH-180427

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180457

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-180452

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

Authors: 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

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

Article Type: Research Article

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

DOI: 10.3233/CH-180468

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