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

Authors: Skinner, Sarah | Nader, Elie | Stauffer, Emeric | Robert, Mélanie | Boisson, Camille | Cibiel, Agnès | Foschia, Clément | Feasson, Léonard | Robach, Paul | Millet, Guillaume Y | Connes, Philippe

Article Type: Research Article

Abstract: BACKGROUND: Endurance running events are known to cause inflammation and result in increased cytokine production. However, the effects of ultramarathons on cytokine profiles are not well characterized. OBJECTIVE: The aim of this study was to describe and compare the effects of a trail (40 km) race and an ultra-trail (171 km) race on leukocyte concentrations and cytokine profiles. METHODS: The study was conducted during the Ultra-Trail du Mont Blanc® ultra-marathon running event, and included 11 runners who completed the 40 km trail run and 12 runners who completed the 171 km ultra-trail. Blood samples were taken before and after the …races. RESULTS: Leukocyte concentrations significantly increased after both races. Circulating levels of IL-6, IL-1β, MCP-1, and IFN-γ were significantly higher after the longer race compared to the shorter race. Furthermore, while both races resulted in significant increases in IL-6 and IL-8, only the longer race resulted in significant increases in MIP-1β, IL-7, IL-17a, and IL-4. CONCLUSIONS: These results illustrate that a 171 km ultra-trail race results in greater modulations in cytokine profiles than a traditional trail race. Show more

Keywords: Running, exercise, ultra-trail, inflammation, cytokines profile, leukocytes

DOI: 10.3233/CH-211121

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Caimi, Gregorio | Hopps, Eugenia | Montana, Maria | Urso, Caterina | Carollo, Caterina | Canino, Baldassare | Lo Presti, Rosalia

Article Type: Research Article

Abstract: The goal of this research was to evaluate the plasma concentration of MMP-9 and its tissue inhibitor (TIMP-1) in different clinical conditions. It included several groups of subjects: 31 overweight subjects; 91 obese adults divided into two subgroups according to the BMI value (BMI 30–35 Kg/m2 and BMI >  35 Kg/m2 ); 90 subjects with metabolic syndrome (MS) divided into two subgroups (with and without diabetes mellitus); 100 subjects with preclinical carotid atherosclerosis (PCA) divided according to the number of cardiovascular risk factors and to the insulin resistance degree; 48 subjects with obstructive sleep apnoea syndrome (OSAS) divided according to the apnoea/hypopnea index …(AHI); 27 subjects with chronic kidney disease (CKD) on conservative management; 31 subjects with CKD on regular haemodialysis treatment. We have found a significant increase of MMP-9 and TIMP-1 in overweight subjects, in obese adult and in MS subjects. In obese adults, the behaviour of these two parameters was not influenced by the degree of obesity, while in the group of MS subjects both these parameters were clearly influenced by the presence of diabetes mellitus. In subjects with PCA, we observed an increase of MMP-9 associated with a significant decrease of TIMP-1; the same trend was found by subdividing the entire group in accordance with the number of cardiovascular risk factors and with the insulin resistance degree. In subjects with OSAS, we noted an increase in MMP-9 and TIMP-1; this increase was more evident in subjects with OSAS having AHI >  30. In individuals with CKD on conservative and haemodialysis treatment we have found, at baseline, a marked increase in MMP-9 and a significant decrease of TIMP-1. In dialyzed subjects, after a standard dialysis session was noted, a significant increase in MMP-9 was associated with a further decrease in TIMP-1. Show more

Keywords: MMP-9, TIMP-1, obesity, metabolic syndrome, preclinical carotid atherosclerosis, OSAS, CKD

DOI: 10.3233/CH-201094

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2021

Authors: Natrus, Larysa | Ryzhko, Irina | Blazquez-Navarro, Arturo | Panova, Tatyana | Zaychenko, Ganna | Klymenko, Olena | Babel, Nina | Bondur, Vitalii

Article Type: Research Article

Abstract: AIM: The aim of this study was to correlate the content of cells with regulatory molecules associated with angiogenesis in wound healing in a rat model of hyperglycemia. We hypothesize that blood neutrophils are the main VEGF source and can stimulate FLT-1 receptor expression, which is the perquisite for efficient neoangiogenesis. MATERIALS AND METHODS: Kinetic studies of the healing dynamics (3, 7, 14, 21 days) of burn wounds on the skin were conducted in white adult male rats. The content of nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), its receptor (Flt-1) in the regenerated tissue …was analyzed by western blot. Numbers of cells associated with the regenerative process and from peripheral blood (PB) were determined. Additionally a bone marrow (BM) myelogram was conducted. RESULTS: The relative number of peripheral blood (PB) neutrophils was found to be associated with the level of VEGF (R  = 0.708) and Flt-1 (R  = 0.472). The relative number of fibroblasts was also associated with VEGF (R  = 0.562), but not with Flt-1. A negative association was found between the number of neutrophils in the regenerated tissue with VEGF (R  = –0.454) and FLT-1 (R  = –0.665). This confirms our hypothesis, that blood neutrophils are the main VEGF producer that stimulate the expression of the FLT-1 receptor subsequently inducing neoangiogenesis. Furthermore, that under hyperglycemic conditions fibroblasts were highly associated with VEGF (R  = 0.800), while negatively associated with FLT-1 (R  = –0.506). There was a high association between PB neutrophils and newly generated tissue cells: neutrophils (R  = 0.717) and macrophages (R  = 0.622), as well as the association between neutrophils and macrophages (R  = 0.798). This is an indication of chronic inflammation and increased transmigration of blood cells to the burned tissue. CONCLUSION: Blood neutrophils are the main producer of VEGF and stimulate the expression of the FLT-1 receptor. In the context of hyperglycemia the imbalance of receptor and ligand associated with angiogenesis indicates for chronic inflammation: VEGF and FLT-1, which facilitates hypoxia, prevents the physiological course of burn wound healing and may be important factors in impaired tissue regeneration in diabetes. Show more

Keywords: Angiogenesis, granulocytes, neutrophils, macrophages, connective tissue, burn wound

DOI: 10.3233/CH-201077

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Schmidt, Jeremias | Kruppa, Philipp | Georgiou, Iacovos | Ghods, Mojtaba

Article Type: Research Article

Abstract: BACKGROUND: When performing large volume liposuction, perioperative management of lipedema patients with coagulation disorders remains challenging due to a lack of clinical experience. With a prevalence of 1 %of von Willebrand disease (VWD) in the general population, basic knowledge on diagnostic and adapted surgical strategies are essential for patients’ safety. OBJECTIVE: Based on a selective literature review, the purpose of this article is to present a standardized algorithm for diagnosis and perioperative treatment of VWD patients undergoing large volume liposuction. METHODS: The databases MEDLINE (via PubMed) and Web of Science were selectively searched with the term …“(((liposuction) OR (surgery)) OR (lipectomy)) AND (((VWD) OR (hemostaseology)) OR (von Willebrand disease))”. Included were articles published in English or German until November 2020. RESULTS: The evidence for large volume liposuctions in patients with VWD is limited. Experience is largely based on operations with similar bleeding risks. A safe performance requires an adjustment of the surgical technique and a customized perioperative drug substitution plan. According to the current literature, perioperative thromboembolic events appear to be rare with adequate drug treatment. CONCLUSION: The implementation of the developed diagnostic and treatment algorithm may help further reducing bleeding complications and improve the safety for treated patients. Show more

Keywords: Lipedema, liposuction, von Willebrand disease, hemostaseology

DOI: 10.3233/CH-201063

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

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

Article Type: Editorial

DOI: 10.3233/CH-219001

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 2021

Authors: Evans, V.J. | Lawrence, M. | Whitley, J. | Johns, C. | Pillai, S. | Hawkins, K. | Power, K. | Morris, K. | Williams, R. | Evans, P.A.

Article Type: Research Article

Abstract: BACKGROUND: The acute vascular disease deep vein thrombosis (DVT) requires oral anticoagulants to prevent progression. Monitoring therapeutic efficacy of direct oral anticoagulants (DOAC), including rivaroxaban, is problematic as no reliable test is available. Advances in rheometry have led to the development of a functional coagulation biomarker using Gel Point (GP) analysis which assesses clot structure formation. The biomarker measures incipient clot formation time (TGP ) and quantifies fibrin clot structure in terms of fractal dimension (df ). OBJECTIVE: This study aimed to investigate clot structure formation in first time DVT and the effect of rivaroxaban treatment. …METHODS: This prospective observational cohort study measured the GP and standard laboratory markers at three sample points: pre-treatment and at 20 and 60 days following 15 mg BD and 20 mg OD rivaroxaban respectively. RESULTS: Forty DVT patients (mean age 64 years [SD±14.8]; 23 males, 17 female) were recruited. The results show that DVT vs non-DVT patients did not have a significantly different GP profile (df : 1.72±0.06 vs 1.70±0.06 and TGP : 267±68 sec vs 262±73 sec) with both within the defined healthy index. In addition, rivaroxaban therapy increased TGP to 392 s (±135 s) after 20 days, and subsequently increased to 395 s (±194 s) at 60 days but did not significantly increase df (from 1.69±0.05 to 1.71±0.06). CONCLUSIONS: The results indicate in this cohort of DVT patients there was no underlying hypercoagulable effect as determined by gel point analysis. Furthermore, the anticoagulant effect of rivaroxaban prolonged clotting, suggesting a protective effect against clot formation, without significantly reducing clot microstructural properties. Show more

Keywords: Rivaroxaban, coagulation inhibitors, venous thrombosis, clot structure, biomarkers

DOI: 10.3233/CH-201030

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Cao, Jiaying | Dong, Yi | Fan, Peili | Mao, Feng | Chen, Kailing | Chen, Rongxin | Huang, Beijian | Cheng, Yaqing | Wang, Wen-Ping

Article Type: Research Article

Abstract: BACKGROUND: Dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) with quantitative analysis is available in recent years. It can reduce the quantitative sampling error caused by the inconsistency of different sections in order to evaluate local treatment response of hepatocellular carcinoma (HCC) accurately. OBJECTIVE: To investigate the value of dynamic 3D-CEUS in evaluating the early response to transarterial chemoembolization (TACE) treatment in patients with advanced HCC lesions. METHODS: In this prospective study, both two-dimensional (2D) CEUS and dynamic 3D-CEUS were performed on 40 HCC patients who scheduled for TACE at baseline (T0) and 1–3 days (T1) after treatment. Tumor …microvascular perfusion changes were assessed by CEUS time-intensity curve (TIC) and quantitative parameters. According to contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging 1 month after treatment results, patients were divided into responders and non-responders groups. The changes of perfusion parameters of both 2D-CEUS and 3D-CEUS were compared between responders and non-responders groups before and after TACE treatment. RESULTS: Before and after TACE treatment, no significant difference in maximum diameter of HCC lesions between the two groups could be found. There were more significant differences and ratios of perfusion parameters in 3D-CEUS quantitative analysis than in 2D-CEUS. The mutual significant differences and ratios of 2D-CEUS and 3D-CEUS included peak intensity (PI) difference, PI ratio, ratio of area under the curve (A), ratio of area under the wash-out part (AWO) and slope (S) difference. The former 4 corresponding parameters were better on 3D-CEUS than on 2D-CEUS. CONCLUSION: Dynamic 3D-CEUS can be used as a potential imaging method to evaluate early treatment response to TACE in advanced HCC patients. Show more

Keywords: Contrast-enhanced ultrasound, advanced, hepatocellular carcinoma, three-dimensional, treatment response

DOI: 10.3233/CH-201086

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Zhao, Shanjun | Yu, Lei

Article Type: Research Article

Abstract: BACKGROUND: Ischemia reperfusion usually results in certain degree of damage to the myocardium, which is called myocardial ischemia/reperfusion (I/R) injury. OBJECTIVE: Previous studies have found that Sirt1 plays a critical role in I/R injury by protecting cardiac function. SRT1460 is the activator for Sirt1 that participates in the regulation of various diseases. However, whether SRT1460 has any effects on myocardial I/R injury needs further study. METHODS: The I/R rat model and H/R H9C2 model were established to simulate myocardial I/R injury. The infarct area of the rat heart was examined through TTC staining. The EF and …FS of rats were detected through echocardiography. The levels of CK-MB, LDH, MDA, SOD and CK in cardiac tissues, serum or H9C2 cells were measured using commercial kits. Cell viability was assessed through MTT assay. Apoptosis was determined through flow cytometry analysis. Sirt1 expression was measured through western blot. RESULTS: Our work found that SRT1460 reduced the infarct area of the heart induced by myocardial I/R injury. In addition, SRT1460 was confirmed to ameliorate cardiac dysfunction induced by myocardial I/R injury. Further exploration discovered that SRT1460 weakened oxidative stress induced by myocardial I/R injury. Findings from in vitro assays demonstrated that SRT1460 relieved injury of H/R-treated H9C2 cells. Finally, rescue assays proved that Sirt1 knockdown reversed the protective effects of SRT1460 on the injury of H/R-treated H9C2 cells. CONCLUSION: Sirt1 activated by SRT1460 protected against myocardial I/R injury. This discovery may offer new sights on the treatment of myocardial I/R injury. Show more

Keywords: Sirt1, SRT1460, myocardial I/R injury

DOI: 10.3233/CH-201061

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Glazkova, P.A. | Kulikov, D.A. | Glazkov, A.A. | Terpigorev, S.A. | Rogatkin, D.A. | Shekhyan, G.G. | Krasulina, K.A. | Kulikov, A.V. | Makmatov-Rys, M.B. | Paleev, F.N.

Article Type: Research Article

Abstract: BACKGROUND: The role of microcirculatory disorders is progressively being accepted in the pathogenesis of cardiovascular diseases. OBJECTIVE: The purpose of current study is to assess whether we can consider skin microcirculation disorders as a biomarker of cardiovascular events. METHODS: Group 1 consisted of healthy volunteers (n  = 31); group 2 (n  = 42) consisted of patients with diseases that increase the risk of cardiovascular events; group 3 (n  = 39) included patients with the history of cardiovascular events. Skin microcirculation measurement was performed using laser Doppler flowmetry during the heating test. RESULTS: LDF parameters reflecting the rapid …response of microcirculation to heating (“Slope 120 s” and “Slope 180 s”) significantly differed in three groups (p  <  0.05). A decrease in the “Slope 180 s” parameter less than 0.5 PU/s is associated with cardiovascular events (sensitivity 69.2%, specificity 66.7%; the area under the ROC curve, 0.667; 95% confidence interval [CI], 0.545–0.788, p  = 0.01). Multivariable logistic regression analysis revealed that “Slope 180 s≤0.5 PU/s” was significantly related to cardiovascular events (adjusted odds ratio = 3.9, p  = 0.019, CI 95% 1.2–12). CONCLUSIONS: Reduced reactivity of the skin microcirculation may be useful as a biomarker of severe damage to the cardiovascular system and is promising as a risk factor for cardiovascular events. Show more

Keywords: Cardiovascular diseases, skin, microcirculation, laser-Doppler flowmetry, risk factors, diabetes mellitus, hypertension

DOI: 10.3233/CH-201016

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Maxeiner, Andreas | Fischer, Thomas | Stephan, Carsten | Treskatsch, Selda | Baur, Alexander Daniel Jacques | Jung, Ernst-Michael | Hamm, Bernd | Lerchbaumer, Markus Herbert

Article Type: Research Article

Abstract: BACKGROUND: Tissue Doppler imaging (TDI) uses the Doppler principle to quantify the movement of biological tissues. OBJECTIVE: To investigate the contribution of TDI parameters derived during magnetic resonance imaging and ultrasound (MRI/US) fusion-guided biopsy for prostate cancer (PCa) discrimination. METHODS: From March 2016 to Dec. 2018, 75 men with suspected PCa prospectively underwent fusion-guided prostate biopsy. TDI overlaid on predefined target lesion were compared to the confirmed contralateral tumor-free area of the prostate gland (using Image J). Diagnostic value of TDI parameters was assessed using histopathology as standard of reference. RESULTS: Thirty-seven patients were …diagnosed with PCa (49.3%), among them 27 with clinically significant PCa (Gleason score >  3 + 3 = 6 (ISUP 1). The LES/REF ratio was lower in confirmed PCa patients compared to patients without PCa (0.42, IQR, 0.22–0.59 vs. 0.52, IQR, 0.40–0.72, p  = 0.017). TDI parameters allowed differentiation of low-risk from high-to-intermediate-risk PCa (ISUP 2 versus ISUP 3) based on lower pixel counts within the target ROI (1340, IQR 596–2430 vs. 2687, IQR 2453–3216, p  = 0.004), lower pixel percentage (16.4 IQR 11.4–29.5 vs. 27.3, IQR 22.1–39.5; p  = 0.005), and lower LES/REF ratios (0.29, IQR 0.19–0.51 vs. 0.52, IQR 0.47–0.74, p  = 0.001). CONCLUSION: TDI of prostate lesions prelocated by MRI discriminates between cancerous and noncancerous lesions and further seems to enable characterization of PCa aggressiveness. This widely available US technique may improve confidence in target lesion localization for tissue sampling. Show more

DOI: 10.3233/CH-201035

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Macedo, Lucas Sousa | Rusig, Renato Polese | Silva, Gustavo Bersani | Cho, Alvaro Baik | Hsiang Wei, Teng | Bernardelli Iamaguchi, Raquel

Article Type: Research Article

Abstract: BACKGROUND: Microsurgical flaps are widely used to treat complex traumatic wounds of upper and lower limbs. Few studies have evaluated whether the vascular changes in preoperative computed tomography angiography (CTA) influence the selection of recipient vessel and type of anastomosis and the microsurgical flaps outcomes including complications. OBJECTIVE: The aim of this study was to evaluate if preoperative CTA reduces the occurrence of major complications (revision of the anastomosis, partial or total flap failure, and amputation) of the flaps in upper and lower limb trauma, and to describe and analyze the vascular lesions of the group with CTA …and its relationship with complications. METHODS: A retrospective cohort study was undertaken with all 121 consecutive patients submitted to microsurgical flaps for traumatic lower and upper limb, from 2014 to 2020. Patients were divided into two groups: patients with preoperative CTA (CTA+) and patients not submitted to CTA (CTA–). The presence of postoperative complications was assessed and, within CTA+, we also analyzed the number of patent arteries on CTA and described the arterial lesions. RESULTS: Of the 121 flaps evaluated (84 in the lower limb and 37 in the upper limb), 64 patients underwent preoperative CTA. In the CTA+ group, 56% of patients with free flaps for lower limb had complete occlusion of one artery. CTA+ patients had a higher rate of complications (p  = 0.031), which may represent a selection bias as the most complex limb injuries and may have CTA indicated more frequently. The highest rate of complications was observed in chronic cases (p  = 0.034). There was no statistically significant difference in complications in patients with preoperative vascular injury or the number of patent arteries. CONCLUSIONS: CTA should not be performed routinely, however, CTA may help in surgical planning, especially in complex cases of high-energy and chronic cases, since it provides information on the best recipient artery and the adequate level to perform the microanastomosis, outside the lesion area. Show more

Keywords: Computed tomography angiography, free flap, microvascular free flap, trauma surgery, complex injuries, complication rates

DOI: 10.3233/CH-200986

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Huemer, Georg

Article Type: Research Article

Abstract: BACKGROUND: The length of the amputation stump is crucial for optimal prosthetic fitting and rehabilitation. Especially in traumatic amputation, direct closure of the stump may be challenging, and bone shortening is frequently needed. To avoid excessive bone shortening, coverage of exposed bone with free flaps is a versatile option. OBJECTIVE: Here we present our experience with the utilization of free flaps from the lower abdomen for the coverage of amputations stumps of the lower extremity. METHODS: Between March 2008 and October 2010, five patients (three female, two male) with complex wounds on amputation stumps of the …lower extremity were treated with a mean age of 50 years (range: 15–72 years). Six abdominal free flaps were performed in five patients (one bilateral case), including four deep inferior epigastric artery (DIEP-) and two muscle-sparing transverse rectus abdominis muscle (ms-TRAM-) flaps. Patient’s and operative data were collected retrospectively. RESULTS: One complete flap failure occurred (overall success rate: 83.3%). Three of five patients gained full ambulatory status. CONCLUSIONS: Due to the low donor site morbidity a long vascular pedicle and the large amount of available tissue, abdominal based free flaps represent our first choice for microsurgical reconstruction of lower extremity stumps. Show more

Keywords: Amputation stump, free flap, lower extremity reconstruction

DOI: 10.3233/CH-211112

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2021

Authors: Zhang, Hui-Li | Zhu, Jing-E | Li, Jia-Xin | Li, Xiao-Long | Sun, Li-Ping | Xu, Hui-Xiong | Yu, Song-Yuan

Article Type: Research Article

Abstract: A 33 years’ old male complained of excessive salivation with frequent swallowing and spitting, which resulted in communication disturbance, reduced quality of life, and social embarrassment for 19 years. He had been diagnosed as sialorrhea and submandibular gland hyperfunction by stomatologist, then had unilateral submandibular gland resection 13 years ago, but the symptom relief was not satisfactory. After that, he had been treated with glycopyrrolate for less than a year, which was withdrawn because of the short duration of symptomatic control after each tablet take-in and intolerable side effects. With the wish to receive a new treatment with long term …effectiveness, low re-operation risk and normal preserved saliva secretion function, the patient was subject to MWA for the right submandibular gland. After systematic clinical evaluation, US-guided percutaneous MWA was successfully performed with an uneventful post-operative course. The volume of the right submandibular gland and ablated area were measured precisely by an ablation planning software system with automatic volume measurement function based on three-dimensional reconstruction of the pre-operative and post-operative enhanced magnetic resonance imaging (MRI) raw data. Finally, the ablated volume was calculated as 62.2% of the whole right submandibular gland. The patient was discharged 1 day after the operation, with symptoms relieved significantly, the mean value of whole saliva flow rate (SFR) decreased from 11 ml to 7.5 ml per 15 minutes. During the follow up by phone three months after operation, the patient reported that the treatment effect was satisfactory, whereas the SFR value became stable as 7 ml per 15 minutes, drooling frequency and drooling severity (DFDS) score decreased from 6 to 5, drooling impact scale (DIS) score decreased from 43 to 26. US-guided percutaneous MWA of submandibular gland seems to be an alternative, minimal invasive, and effective treatment for refractory sialorrhea. We described a patient with refractory sialorrhea treated successfully with ultrasound (US) guided percutaneous microwave ablation (MWA). Show more

DOI: 10.3233/CH-211115

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Matrai, Adam Attila | Varga, Gabor | Tanczos, Bence | Barath, Barbara | Varga, Adam | Horvath, Laszlo | Bereczky, Zsuzsanna | Deak, Adam | Nemeth, Norbert

Article Type: Research Article

Abstract: BACKGROUND: The effects of temperature on micro-rheological variables have not been completely revealed yet. OBJECTIVE: To investigate micro-rheological effects of heat treatment in human, rat, dog, and porcine blood samples. METHODS: Red blood cell (RBC) - buffer suspensions were prepared and immersed in a 37, 40, and 43°C heat-controlled water bath for 10 minutes. Deformability, as well as mechanical stability of RBCs were measured in ektacytometer. These tests were also examined in whole blood samples at various temperatures, gradually between 37 and 45°C in the ektacytometer. RESULTS: RBC deformability significantly worsened in the samples …treated at 40 and 43°C degrees, more expressed in human, porcine, rat, and in smaller degree in canine samples. The way of heating (incubation vs. ektacytometer temperation) and the composition of the sample (RBC-PBS suspension or whole blood) resulted in the different magnitude of RBC deformability deterioration. Heating affected RBC membrane (mechanical) stability, showing controversial alterations. CONCLUSION: Significant changes occur in RBC deformability by increasing temperature, showing inter-species differences. The magnitude of alterations is depending on the way of heating and the composition of the sample. The results may contribute to better understanding the micro-rheological deterioration in hyperthermia or fever. Show more

Keywords: Hyperthermia, fever, heat-treatment, hemorheology, interspecies differences

DOI: 10.3233/CH-211118

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Barath, Barbara | Somogyi, Viktoria | Tanczos, Bence | Varga, Adam | Bereczky, Zsuzsanna | Nemeth, Norbert | Deak, Adam

Article Type: Research Article

Abstract: BACKGROUND: Red blood cell (RBC) aggregation plays an important role in the physiological processes of the microcirculation. The complete mechanism of aggregation is still unclear, and it is influenced by several cellular and plasmatic factors. One of these factors is the hematocrit (Hct). OBJECTIVE: We hypothesized that the relation of RBC aggregation and Hct differs between species. METHODS: From anticoagulated blood samples of healthy volunteers, rats, dogs, and pigs, 20, 40, and 60 %Hct RBC, autologous plasma suspensions were prepared. Hematological parameters and RBC aggregation was determined by light-transmission and light-reflection method. RESULTS: Suspensions …at 20%and 60%Hct expressed lower RBC aggregation than of 40%Hct suspensions, showing inter-species differences. By curve fitting the Hct at the highest aggregation value differed in species (human: 45.25%- M 5 s, 40.86%- amp;rat: 44.44 %- M1 10 s, 39.37%- amp; dog: 42.48%- M 5 s, 44.29%- amp; pig: 47.63%- M 5 s, 52.8%- amp). CONCLUSION: RBC aggregation - hematocrit relation shows inter-species differences. Human blood was found to be the most sensitive for hematocrit changes. The more obvious differences could be detected by M 5 s by light-transmission method and amplitude parameter using light-reflection method. Show more

Keywords: Hemorheology, red blood cell aggregation, hematocrit, inter-species differences

DOI: 10.3233/CH-211109

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Wu, Junyuan | Li, Zhiwei | Yuan, Wei | Zhang, Qiang | Liang, Yong | Zhang, Mingqing | Qin, Hongjie | Li, Chunsheng

Article Type: Research Article

Abstract: BACKGROUND: Shenfu injection (SFI) is a traditional Chinese herbal medicine which has been clinically used for treatment of septic shock and cardiac shock. The aim of this study was to clarify effects of SFI on cerebral microcirculation and brain injury after hemorrhagic shock (HS). METHODS: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n  = 8), saline group (SA, n  = 8) or sham operation group (SO, n  = 5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained …at 40±3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin-6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured. RESULTS: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin-6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group. CONCLUSIONS: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury. Show more

Keywords: Hemorrhagic shock, shenfu injection, microcirculation, microvascular endothelium, brain injury

DOI: 10.3233/CH-211100

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Zhang, Chao | Yin, Jing | Hu, Chenlu | Ye, Qin | Wang, Ping | Huang, Pintong

Article Type: Research Article

Abstract: PURPOSE: The aim of this study was to evaluate the efficacy, safety and costs of ultrasound guided percutaneous radiofrequency ablation (RFA) versus open thyroidectomy for treating low-risk papillary thyroid microcarcinoma (PTMC) by using propensity score matching (PSM). PATIENTS AND METHODS: 157 patients who underwent RFA and 206 patients who underwent surgery for low-risk PTMC were included in the study. The patients were followed up at 1, 3, 6, 12 months after treatment, and every half year thereafter. A 1:1 PSM method was applied to balance the pretreatment data of the two groups. In the matched group (133 patients …for each), the operative time, length of hospital stay, hospitalization expenses, cosmetic results, complications were assessed and compared between two groups. RESULTS: At last follow-up, 39 tumors (29.3%) in the RFA group completely disappeared. Between the well-matched groups, no local recurrence, lymph node metastasis or distant metastases were detected in either group during the follow-up period. After matching, the operation time and hospitalization time in RFA group were shorter than those in surgery group (both P  <  0.05). The average hospitalization expense of the patients in RFA group was cheaper than that in surgery group (P  <  0.05). Moreover, the cosmetic score was found to be higher in RFA group than that observed in surgery group (P  <  0.05). CONCLUSIONS: RFA may be an effective and safe method for treating low-risk PTMC with a superior advantage of being low-cost and having a shorter operation time and hospital stay versus surgery. Show more

Keywords: Papillary thyroid microcarcinoma, radiofrequency ablation, ultrasound, thyroidectomy

DOI: 10.3233/CH-201087

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Guan, Pei-Shan | Yuan, Hai-Xia | Wang, Wen-Ping

Article Type: Research Article

Abstract: Gallbladder cancer is a malignant tumor with high mortality. Early diagnosis is significance to improve the prognosis of patients. Gallbladder adenoma is recognized as a kind of precancerous disease, for the past few years, contrast-enhanced ultrasound was used in the diagnosis of biliary tumors. This case is about gallbladder papillary adenoma with carcinogenesis. There is rare literature on the contrast-enhanced ultrasound manifestations of this type of disease. We hope that this report can help improve the recognition of contrast-enhanced ultrasound features and improve the accuracy of early diagnosis of gallbladder cancer.

Keywords: Gallbladder cancer, papillary adenoma, carcinogenesis, contrast-enhanced ultrasound

DOI: 10.3233/CH-200940

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2021

Authors: Deng, Wen-Fang

Article Type: Research Article

Abstract: OBJECTIVE: To compare the diagnostic efficacy of ACR TI-RADS, Kwak TI-RADS, ATA guidelines and KTA/KSThR guidelines in combination with shear wave elastography (SWE) for thyroid nodules. METHODS: The retrospective study included 566 thyroid nodules with maximum diameter≥5 mm which confirmed by FNA cytology or/and surgical pathology. The sensitivity, specificity, accuracy, Youden index of diagnosis of thyroid nodules by ACR TI-RADS, Kwak TI-RADS, ATA guidelines, KTA/KSThR guidelines and SWE were calculated. The ROC curve was drawn to determine the cut-off values of the four ultrasound classification systems and SWE Emax. The diagnostic efficacy of the four ultrasound classification systems …in combination with SWE were calculated and compared with those of pre-combination. RESULTS: The ROC curves indicated that the cut-off value of ACR TI-RADS, Kwak TI-RADS, ATA guidelines, KTA/KSThR guidelines and Emax of SWE was TR5, 4c, high-suspicion, high-suspicion, and 41.7 kPa, respectively, and the area under the ROC curve (AUC) was 0.907(0.879–0.934), 0904(0.876–0.932), 0.894(0.863–0.924), 0.888(0.856–0.919), 0.886(0.859–0.913), respectively. After combination with SWE, the the sensitivities of the four ultrasound classification systems for the diagnosis of nodules were improved, and the differences were statistically significant (all P ≤0.001); the specificities were decreased, but the differences were not statistically significant (all P  >  0.05); the accuracies were improved, but only the difference of ACR TI-RADS was statistically significant (x2  = 4.45, p  = 0.035); the differences in the AUCs were not significant (all P  >  0.05). CONCLUSIONS: The four ultrasound classification systems and SWE all had high performance in the diagnosis of thyroid nodules. The four classification systems in combination with SWE were all beneficial to the differential diagnosis of nodules, and ACR TI-RADS in combination with SWE was more effective, especially for TR3 and TR4 nodules. Show more

Keywords: Thyroid nodules, thyroid ultrasound classification system, thyroid imaging reporting and data system, shear wave elastography

DOI: 10.3233/CH-201021

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Xing, Yinting | Yang, Wei | Jin, Yingyu | Wang, Chao | Guan, Xiuru

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: To study whether D-dimer daily continuous tendency could predict the short-term prognosis of COVID-19. PATIENTS AND METHODES: According to the short-term prognosis, 81 COVID-19 patients were divided into two groups, one of worse prognosis (Group W) and the other of better prognosis (Group B). The slope of D-dimer linear regression during hospitalization (SLOPE) was calculated as an indicator of D-dimer daily continuous tendency. The SLOPE difference between Group W and Group B was compared. The difference between the discharge results and the 3-month follow-up results was also compared. COX regression analysis was used to analyze …the relationship between SLOPE and short-term prognosis of COVID-19. RESULTS: There were 16 patients in Group W and 65 patients in Group B. Group W had more critical proportion (p  <  0.0001), indicating that the symptoms of its patients were more severe during hospitalization. ARDS, the most visible cause of worse prognosis, accounted for up to 68.75%, and many symptoms merged and resulted in worse prognosis. The D-dimer levels of Group W not only were significantly higher (p  <  0.0001), but also showed an increasing trend. In addition, the D-dimer levels at discharge were significantly higher than those at follow-up (p  = 0.0261), and the mean difference was as high as 0.7474. SLOPE significantly correlated with the short-term prognosis of COVID-19 independently (RR: 1.687, 95% CI: 1.345–2.116, P  <  0.0001). The worst prognosis occurred most likely during the first month after COVID-19 diagnosis. CONCLUSION: Our study found that D-dimer daily continuous tendency independently correlates with worse prognosis and can be used as an independent predictor of the short-term prognosis for COVID-19. Show more

Keywords: Coronavirus disease 2019 (COVID-19), SARS-CoV-2, D-dimer, prognosis, nomogram

DOI: 10.3233/CH-201071

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Krüger-Genge, A. | Steinbrecht, S. | Jung, C.G.H. | Westphal, Sophia | Klöpzig, Stefanie | Waldeck, P. | Küpper, J.-H. | Storsberg, J. | Jung, F.

Article Type: Research Article

Abstract: Within the last years a comprehensive number of scientific studies demonstrated beneficial effect of Arthropira platensis (AP ) as dietary supplement due to a high content of proteins, minerals and vitamins. Positive effects like promoting the immune system, reducing inflammation and an anti-oxidant capacity are reported. In this study, the effect of an aqueous AP extract on primary human venous endothelial cells (HUVEC) was investigated. In addition, the effect of AP on HUVEC treated with a bacterial toxin (lipopolysaccharide, LPA), inducing an activation of HUVEC and cellular detachment, was analyzed. Depending on the concentration of AP …extract a significantly accelerated formation of an endothelial cell monolayer was observed. Furthermore, the detachment of HUVEC after LPA addition was dramatically reduced by AP. In conclusion, the data are promising and indicatory for an application of Arthrospira platensis in the clinical field. Show more

Keywords: Arthrospira platensis – endothelial cells – xCELLigence system

DOI: 10.3233/CH-201096

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Chen, Ye | Wang, Shouhong | Huang, Jianrong | Fu, Yingyun | Wen, Juanmin | Zhou, Chengbin | Fu, Yang | Liu, Lei

Article Type: Research Article

Abstract: INTRODUCTION: Coronavirus disease-19 (COVID-19) is a new type of epidemic pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The population is generally susceptible to COVID-19, which mainly causes lung injury. Some cases may develop severe acute respiratory distress syndrome (ARDS). Currently, ARDS treatment is mainly mechanical ventilation, but mechanical ventilation often causes ventilator-induced lung injury (VILI) accompanied by hypercapnia in 14% of patients. Extracorporeal carbon dioxide removal (ECCO2R) can remove carbon dioxide from the blood of patients with ARDS, correct the respiratory acidosis, reduce the tidal volume and airway pressure, and reduce the incidence of VILI. …CASE REPORT: Two patients with critical COVID-19 combined with multiple organ failure undertook mechanical ventilation and suffered from hypercapnia. ECCO2R, combined with continuous renal replacement therapy (CRRT), was conducted concomitantly. In both cases (No. 1 and 2), the tidal volume and positive end-expiratory pressure (PEEP) were down-regulated before the treatment and at 1.5 hours, one day, three days, five days, eight days, and ten days after the treatment, together with a noticeable decrease in PCO2 and clear increase in PO2, while FiO2 decreased to approximately 40%. In case No 2, compared with the condition before treatment, the PCO2 decreased significantly with down-regulation in the tidal volume and PEEP and improvement in the pulmonary edema and ARDS after the treatment. CONCLUSION: ECCO2R combined with continuous blood purification therapy in patients with COVID-19 who are criti-cally ill and have ARDS and hypercapnia might gain both time and opportunity in the treatment, down-regulate the ventilator parameters, reduce the incidence of VILI and achieve favorable therapeutic outcomes. Show more

Keywords: Coronavirus disease-19, multiple organ failure, hypercapnia, continuous blood purification, extracorporeal carbon dioxide removal

DOI: 10.3233/CH-201080

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Yang, Wen-qi | Cui, Xiao-lan | Zhang, Ming | Yuan, Xiao-dong | Ying, Liang | Li, Feng-hua | Li, Hong-li

Article Type: Research Article

Abstract: OBJECTIVE: To assess iliac blood vessels using conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) before kidney transplantation (KT) and determine whether US findings related to post-transplant outcomes. METHODS: A total of 119 patients received US and CEUS before KT waiting-list acceptance. The preoperative iliac blood hemodynamics and vascular conditions were evaluated. The operative strategy and follow-up outcomes were recorded. Logistic regression and correlation analysis were used. The accuracy in determining the patency of iliac blood vessels was calculated before and after the injection of contrast materials. RESULTS: CEUS can help to significantly improve the visualization of …the internal iliac artery, but there was no significant correlation with post-transplant outcomes. In terms of accuracy, there were significant differences in determining the patency of internal iliac arteries between conventional US and CEUS (60.5% and 100%, p  <  0.001). The surgical strategy of one patient was regulated and two patients were excluded from KT according to US findings. CONCLUSIONS: Compared with conventional US, CEUS helps to improve the visualization of the internal iliac artery. Conventional US and CEUS have the potential to serve as effective methods to evaluate anatomy and hemodynamics of iliac vessels and have a potential value while defining clinical algorithms in surgery decision-making. Show more

Keywords: Contrast-enhanced ultrasonography, ultrasound, kidney transplantation, iliac artery

DOI: 10.3233/CH-201054

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Kexin, Song | Mingzi, Zhang | Hao, Liu | Yan, Hao | Zheng, Qi | Cheng, Feng | Youbin, Wang

Article Type: Research Article

Abstract: OBJECTIVE: Here we examined the influence of methane-rich saline treatment (MS) on the whole transcriptome of the skin flaps during the ischemia/reperfusion (I/R) injuryusing RNA-sequence (RNA-seq). METHODS: The rats were divided into three groups: the sham surgery group (SH),the I/R surgery group treated with physiological saline (I/R-P) or the I/R surgery group treated with the methane-rich saline (I/R-M) respectively. On the 72 hours after operation, the perfusion and the distribution of micro-circulatoryblood flow in skin flaps were observed by laser doppler flowmeters. The whole transcriptome alteration of the skin flaps was examined using RNA-seq. Moreover, the responses of …the skin flaps to MRS treatment were examined using bio-informatic and q-PCR approaches after I/R injury. RESULTS: The methane-rich saline (MS) treatment could expand survival area and improve the blood perfusion of the skin flaps after l/R injury. Compared to the I/R-P group, 474 genes significantly altered in the I/R-M group. These genes were mainly associated the development, the cell adhesion and migration. In addition, the PI3K-Akt signal pathway was meaningfully related to regulation of MS treatment. Q-PCR results confirmed that MS treatment positively regulated PI3K-Akt signal pathway relative genes and inhibited the cell adhesion relative genes. CONCLUSION: These results proved that methane-rich saline may alleviate I/R injury and improve flap survival rate by regulating cell adhesion and PI3K-Akt signal pathway. Show more

Keywords: Methane-rich saline, Ischemia/reperfusion injury, skin flaps, cell adhesion, PI3K-Akt signal pathway

DOI: 10.3233/CH-201046

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Zhang, Zheng | Zhao, Shuangshuang | Wang, Keke | Shang, Mengyuan | Chen, Zheming | Yang, Haizhen | Chen, Yanwei | Chen, Baoding

Article Type: Research Article

Abstract: Integrated analysis of accumulated data is an effective way to obtain reliable potential diagnostic molecular of cervical lymph node metastases (LNM) in papillary thyroid carcinoma (PTC). The benefits of prophylactic lymph node dissection (PLND) for these clinically node-negative (cN0) patients remained considerable controversies. Hence, elucidation of the mechanisms of LNM and exploration of potential biomarkers and prognostic indicators are essential for accurate diagnosis of LNM in PTC patients. Up to date, advanced microarray and bioinformatics analysis have advanced an understanding of the molecular mechanisms of disease occurrence and development, which are necessary to explore genetic changes and identify potential diagnostic …biomarkers. In present study, we performed a comprehensive analysis of the differential expression, biological functions, and interactions of LNM-related genes. Two publicly available microarray datasets GSE60542 and GSE129562 were available from Gene Expression Omnibus (GEO) database. Differentially expressed genes between clinically node-positive (cN1) and cN0 PTC samples were screened by an integrated analysis of multiple gene expression profile after gene reannotation and batch normalization. Our results identified 48 differentially expressed genes (DEGs) genetically associated with LNM in PTC patients. Gene ontology (GO) analyses revealed the changes in the modules were mostly enriched in the regulation of MHC class II receptor activity, the immune receptor activity, and the peptide antigen binding. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs displayed the intestinal immune network for IgA production, staphylococcus aureus infection, and cell adhesion molecules (CAMs). To screen core genes related to LNM of PTC from the protein-protein interaction network, top 10 hub genes were identified with highest scores. Our results help us understand the exact mechanisms underlying the metastasis of cervical LNM in PTC tissues and pave an avenue for the progress of precise medicine for individual patients. Show more

Keywords: Lymph node metastasis (LNM), papillary thyroid carcinoma (PTC), hub genes, protein-protein interaction network (PPI)

DOI: 10.3233/CH-201074

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Werner, Jens Martin | Zidek, Martin | Kammerer, Sylvia | da Silva, Natascha Platz Batista | Jung, Friedrich | Schlitt, Hans Jürgen | Hornung, Matthias | Jung, Ernst-Michael

Article Type: Research Article

Abstract: OBJECTIVE: To assess the impact and procedural input of intraoperative ultrasound (IOUS) with contrast-enhanced ultrasound (CEUS) and ultrasound elastography on surgical decision making during the procedure and consequently the out-come after hepato-pancreatico-biliary (HPB) surgery. MATERIALS AND METHODS: Data of 50 consecutive patients, who underwent HPB surgery from 04/2018 to 07/2018 were prospectively collected for this study. During surgery, IOUS with a high-resolution ultrasound device using CEUS after bolus injection of 2.4–5 ml Sulphur hexafluoride microbubbles using a 6–9 MHz probe and a share wave and strain elastography was performed by an experienced examiner. Process and time analysis were carried out …using mobile phone timer. RESULTS: The IOUS with CEUS and elastography correctly identified 42 malignant tumors and 4 benign lesions. In 3 cases, the examination provided false positive result (identifying 3 benign lesions as malignant) and in 1 case a malignant lesion was incorrectly assessed as benign (sensitivity 97,7%, specificity 57,1%, PPV 93,3% and NPV 80%). The specific question by the surgeon could be answered successfully in 98% of the cases. In 76% of the cases, there was a modification (42%) or a fundamental change (34%) of the planned surgical approach due to the information provided by the IOUS. Within the last group, the IOUS had a major impact on therapy outcome. In 7 patients an additional tumor resection was required, in 5 patients the tumor was assessed as inoperable, and in total in 5 patients an intraoperative RFA (4/5) or postoperative RITA (1/5) was required. Regarding procedural input, there was only a slight, but significant difference between the transport and set-up times before the intraoperative use (mean: 14 min 22 s) and the return transport (mean 13 min 6 s), (p  = 0,038). The average examination time was 14 minutes, which makes only one third of the overall time demand. CONCLUSION: Combination of IOUS with CEUS and elastography in oncological HPB surgery provides valuable information that affects surgical decision-making. The procedural input of about 45 minutes seems to be a good investment considering the improvement of the surgical procedure and a significant modification of the therapy approach in the majority of the cases. Show more

Keywords: Surgical decision-making, hepato-pancreatico-biliary surgery, CEUS, elastography

DOI: 10.3233/CH-201031

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

Authors: Troeltzsch, Daniel | Shnayien, Seyd | Gaudin, Robert | Bressem, Keno | Kreutzer, Kilian | Heiland, Max | Hamm, Bernd | Niehues, Stefan

Article Type: Research Article

Abstract: BACKGROUND: Post-therapeutic tissue is bradytrophic and thus has low perfusion values in PCT. In contrast, malignant tissue is expected to show higher perfusion values as cancer growth partially depends on angiogenesis. OBJECTIVES: This prospective study investigates perfusion computed tomography (PCT) for the post-therapeutic detection of cancer in the head and neck region. METHODS: 85 patients underwent PCT for 1) initial work-up of head and neck cancer (HNC; n =22) or 2) for follow-up (n =63). Regions of interest (ROIs) were placed in confirmed tumour, a corresponding location of benign tissue, and reference tissue. Perfusion was calculated …using a single input maximum slope algorithm. Statistical analysis was performed with the Mann-Whitney U-test. RESULTS: PCT allowed significant differentiation of malignant tissue from post-therapeutic tissue after treatment for HNC (p =0.018). Significance was even greater after normalization of perfusion values (p =0.007). PCT allowed highly significant differentiation of HNC from reference tissue (p <0.001). CONCLUSIONS: PCT provides significantly distinct perfusion values for malignant and benign as well as post-therapeutically altered tissue in the head and neck area, thus allowing differentiation of cancer from healthy tissue. Our results show that PCT in conjunction with a standard algorithm is a potentially powerful HNC diagnostic tool. Show more

DOI: 10.3233/CH-200919

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Kim, Kwan Wook | Kim, Sang Woo | Lim, Soyeon | Yoo, Kyung-Jong | Hwang, Ki-Chul | Lee, Seahyoung

Article Type: Research Article

Abstract: Hexokinase 2 (HK2) is a metabolic sensor that couples glycolysis and oxidative phosphorylation of mitochondria by binding to the outer mitochondrial membrane (OMM), and it also has been implicated in induction of apoptotic process by regulating the integrity of OMM. When HK2 detaches from the mitochondria, it triggers permeability increase of the OMM and subsequently facilitates the cytosolic release of cytochrome c, a major apoptosis-inducing factor. According to previous studies, a harsh microenvironment created by ischemic heart disease such as low tissue oxygen and nutrients, and increased reactive oxygen species (ROS) can cause cardiomyocyte apoptosis. Under these conditions, the expression …of HK2 in heart significantly decrease and such down-regulation of HK2 was correlated to the increased apoptosis of cardiomyocytes. Therefore, prevention of HK2 down-regulation may salvage cardiomyocytes from apoptosis. MicroRNAs are short, non-coding RNAs that either inhibit transcription of target mRNAs or degrade the targeted mRNAs via complementary binding to the 3’UTR (untranslated region) of the targeted mRNAs. Since miRNAs are known to be involved in virtually every biological processes, it is reasonable to assume that the expression of HK2 is also regulated by miRNAs. Currently, to my best knowledge, there is no previous study examined the miRNA-mediated regulation of HK2 in cardiomyocytes. Thus, in the present study, miRNA-mediated modulation of HK2 during ROS (H2 O2 )-induced cardiomyocyte apoptosis was investigated. First, the expression of HK2 in cardiomyocytes exposed to H2 O2 was evaluated. H2 O2 (500μM) induced cardiomyocyte apoptosis and it also decreased the mitochondrial expression of HK2. Based on miRNA-target prediction databases and empirical data, miR-181a was identified as a HK2-targeting miRNA. To further examine the effect of negative regulation of the selected HK2-targeting miRNA on cardiomyocyte apoptosis, anti-miR-181a, which neutralizes endogenous miR-181a, was utilized. Delivery of anti-miR-181a significantly abrogated the H2 O2 -induced suppression of HK2 expression and subsequent disruption of mitochondrial membrane potential, improving the survival of cardiomyocytes exposed to H2 O2 . These findings suggest that miR-181a-mediated down-regulation of HK2 contributes to the apoptosis of cardiomyocytes exposed to ROS. Neutralizing miR-181a can be a viable and effective means to prevent cardiomyocyte from apoptosis in ischemic heart disease. Show more

Keywords: Hexokinase 2, miR-181a, reactive oxygen species, ischemic heart disease, cardiomyocytes, apoptosis

DOI: 10.3233/CH-200924

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Wilma, Schierling | Kathrin, Bachleitner | Piotr, Kasprzak | Thomas, Betz | Alexander, Stehr | Karin, Pfister

Article Type: Research Article

Abstract: BACKGROUND: Acute lower limb ischemia (ALI) is associated with a high risk of limb loss and death. OBJECTIVE: The present study evaluates the safety of intraoperative, local urokinase lysis in patients with ALI and crural artery occlusion. METHODS: A total of 107 patients (115 legs) were treated surgically for ALI with additional intraoperative urokinase lysis to improve the outflow tract. Minor and major bleeding as well as efficacy of treatment and amputation-free survival were investigated. RESULTS: Complete restoration of at least one run-off vessel was achieved in 64%. Collateralization was improved in 34%. Lysis …failed in 2%. Major amputation rate was 27%overall (12%within 30 days) and depended on Rutherford class of ALI (overall/30 day: IIa 11%/6%; IIb 20%/17%; III 37%/15%). Amputation-free survival turned out to be 82%after 30 days, 58%after one, and 41%after five years. Minor bleeding occurred in 21%(24/115) and major bleeding in 3.5%(4/115). One of these patients died of haemorrhage. No patient experienced intracranial bleeding. CONCLUSION: Intraoperative urokinase lysis improves limb perfusion and causes low major and intracranial bleeding. It can be safely applied to patients with severe ischaemia when surgical restoration of the outflow tract fails. Show more

Keywords: Acute limb ischemia, bleeding, lysis, safety, thrombectomy, urokinase

DOI: 10.3233/CH-201049

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Lei, Weijuan | Lin, Juliar | Liu, Fang | Chen, Nina

Article Type: Research Article

Abstract: PURPOSE: Acute myeloid leukemia (AML) is a type of hematologic malignancy. This study was attempt to explore the effect of long noncoding RNA GAS6 antisense RNA1 (GAS6-AS1) on pediatric AML and the regulation mechanisms. METHODS: GAS6-AS1, microRNA-370-3p (miR-370-3p), and Tetraspanin3 (TSPAN3) expression in bone marrow (BM) tissues and cells was determined by qRT-PCR. The correlation between GAS6-AS1 and clinicopathological features of pediatric patients with AML was assessed. In vitro , viability and migration and invasion of AML cells were evaluated via MTT and transwell assays, respectively. Interactions among GAS6-AS1, miR-370-3p, and TSPAN3 were revealed by dual-luciferase reporter assays. …Western blot was applied to confirm the protein expression of TSPAN3. RESULTS: GAS6-AS1 and TSPAN3 expression was elevated in BM tissues of pediatric patients with AML and AML cells, but miR-370-3p expression was reduced. GAS6-AS1 expression was positively related to French-American-British (FAB) classification in pediatric patients with AML. In vitro , GAS6-AS1 deficiency restrained the viability, migration, and invasion of AML cells. Additionally, GAS6-AS1 mediated miR-370-3p expression indeed and TSPAN3 was identified as a target of miR-370-3p. Furthermore, miR-370-3p overexpression repressed the protein expression of TSPAN3. The feedback experiments demonstrated that miR-370-3p inhibition or TSPAN3 overexpression mitigated the suppressive effect of sh-GAS6-AS1 on the tumorigenesis of AML cells. CONCLUSION: GAS6-AS1 silencing restrained AML cell viability, migration, and invasion by targeting miR-370-3p/TSPAN3 axis, affording a novel therapeutic target for pediatric AML. Show more

Keywords: GAS6-AS1, acute myeloid leukemia, viability, miR-370-3p, TSPAN3

DOI: 10.3233/CH-201039

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Wiesinger, Isabel | Jung, Friedrich | Jung, Ernst Michael

Article Type: Research Article

Abstract: The external perfusion software (VueBox™ ) for contrast-enhanced ultrasound (CEUS), enables the quantitative analysis of micro-vascularization within non-cystic lesions in terms of characterization and detection. This review summarizes our work about parathyroid gland, thyroid gland, liver, prostate and other tissues as well as original studies in the use of parametric perfusion imaging. Useful perfusion parameters are introduced.

DOI: 10.3233/CH-201040

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Lian, Kai-Mei | Lin, Teng

Article Type: Research Article

Abstract: BACKGROUND: Researchers have evaluated the VTI value in the diagnosis of breast lesions, mostly based on gray-scale. PURPOSE: This study aimed to evaluate the value of color-map virtual touch tissue imaging (CMV) in the diagnosis of breast lesions. METHODS: We retrospectively analyzed the virtual touch tissue imaging (VTI) images of 55 breast lesions in 49 female patients who underwent an examination of breast lesions in our hospital from January 2019 to December 2019. The pathological results were taken as the gold standard. The receiver operating characteristic (ROC) curve of CMV was analyzed, and its diagnostic performance …was evaluated. Weighted Kappa (k ) statistics were used to assess the inter-observer agreement for CMV. RESULTS: A total of 55 breast lesions were included, including 19 malignant lesions and 36 benign lesions. Multivariate analysis showed that patients with higher CMV scores (P  = 0.014, odds ratio [OR] = 13.667, 95% CI = 1.702–109.773) were independent predictors of breast cancer. The sensitivity, specificity, and the area under curve (AUC) of CMV were 94.47%, 72.22%, and 0.912. The CMV’s inter-observer agreement was almost perfect among radiologists with different work experience (k  = 0.854, standard error = 0.049, 95% confidence interval = 0.758–0.950). CONCLUSIOS: CMV has high accuracy and repeatability in the diagnosis of malignant breast lesions. Show more

Keywords: Breast lesion, ultrasound, elastography

DOI: 10.3233/CH-201088

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2021

Authors: Farber, Paulo Luiz

Article Type: Research Article

Abstract: Low plasma estrogens, vitamin D deficiency, obesity, diabetes, cardiovascular diseases, thromboembolism, and impaired microcirculation are linked to the severity of covid-19. Studies have suggested that these comorbidities also are related to erythrocyte factors linked to increased blood viscosity in microcirculation such as erythrocyte aggregation and erythrocyte deformability. Increased blood viscosity in microcirculation can lead to a decrease in oxygenation and nutrition of tissues. Therefore erythrocyte aggregation and erythrocyte deformability may be involved in covid-19 severity, leading to tissue hypoxia and a decrease of drug concentration in affected organs. If this relationship is demonstrated, erythrocytes factors can be used to monitor …treatments for improve microcirculatory fluidity that may decrease covid-19 severity. Lifestyle improvement and treatments such as vitamin D and estrogens supplementation are some possible approaches to improve microcirculation and covid-19 prevention and treatment. Show more

Keywords: Covid-19, hemorheology, microcirculation, estrogen, diabetes, vitamin D, obesity, cardiovascular diseases

DOI: 10.3233/CH-201082

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2021

Authors: Ashraf, Fahmida | Ambreen, Tehmina | Park, Cheol Woo | Kim, Dong-ik

Article Type: Research Article

Abstract: PURPOSE: Cross limb stent graft (SG) configuration technique for endovascular aneurysm repair (EVAR) is employed for splayed aortic bifurcations to avoid device kinking and smoothen cannulation. The present study investigates three types of stent graft (SG) configurations for endovascular aneurysm repair (EVAR) in abdominal aortic aneurysm. A computational fluid dynamic analysis was performed on the pulsatile non-Newtonian flow characteristics in three ideally modeled geometries of abdominal aortic (AA) SG configurations. METHODS: The three planar and crosslimb SG configurations were ideally modeled, namely, top-down nonballet-type, top-down ballet-type, and bottom-up nonballet-type configurations. In top-down SG configuration, most of the device …is deployed in the main body in the vicinity of renal artery and the limbs are extended to the iliac artery. While in the bottom-up configuration, some of the SG device is deployed in the main body, the limbs are deployed in aortic bifurcation, and the extra stent graft of the main body is extended to the proximal aorta until the below of the renal artery. The effects of non-Newtonian pulsatile flow on the wall stresses and flow patterns of the three models were investigated and compared. Moreover, the average wall shear stress (AWSS), oscillatory shear stress index (OSI), absolute helicity, pressure distribution, graft displacement and flow visualization plots were analyzed. RESULTS: The top-down ballet-type showed less branch blockage effect than the top-down nonballet-type models. Furthermore, the top-down ballet-type configuration showed an increased tendency to sustain high WSS and higher helicity characteristics than that of the bottom-up and top-down non-ballet type configurations. However, displacement forces of the top-down ballet-type configuration were 40%and 9.6%higher than those of the bottom-up and top-down nonballet-type configurations, respectively. CONCLUSIONS: Some complications such as graft tearing, thrombus formation, limb disconnection during long term follow up periods might be relevant to hemodynamic characteristics according to the configurations of EVAR. Hence, the reported data required to be validated with the clinical results. Show more

Keywords: Abdominal aortic aneurysm, EVAR, hemodynamics, non-newtonian flow

DOI: 10.3233/CH-200996

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-27, 2021

Authors: Dong, Yi | Qiu, Yijie | Yang, Daohui | Yu, Lingyun | Zuo, Dan | Zhang, Qi | Tian, Xiaofan | Wang, Wen-Ping | Jung, Ernst Michael

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the clinical value of dynamic contrast enhanced ultrasound (D-CEUS) in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In this retrospective study, 16 patients with surgery and histopathologically proved HCC lesions were included. Patients were classified according to the presence of MVI: MVI positive group (n  = 6) and MVI negative group (n  = 10). Contrast enhanced ultrasound (CEUS) examinations were performed within a week before surgery. Dynamic analysis was performed by VueBox ® software (Bracco, Italy). Three regions of interests (ROIs) were set in the center of HCC lesions, at the margin …of HCC lesions and in the surrounding liver parenchyma accordingly. Time intensity curves (TICs) were generated and quantitative perfusion parameters including WiR (wash-in rate), WoR (wash-out rate), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiPi (wash-in perfusion index) were obtained and analyzed. RESULTS: All of HCC lesions showed arterial hyperenhancement (100 %) and at the late phase as hypoenhancement (75 %) in CEUS. Among all CEUS quantitative parameters, the WiAUC and WoAUC were higher in MVI positive group than in MVI negative group in the center HCC lesions (P  <  0.05), WiAUC, WoAUC and WiPI were higher in MVI positive group than in MVI negative group at the margin of HCC lesions. WiR and WoR were significant higher in MVI positive group. CONCLUSIONS: D-CEUS with quantitative perfusion analysis has potential clinical value in predicting the existence of MVI in HCC lesions. Show more

Keywords: Dynamic contrast enhanced ultrasound (D-CEUS), hepatocellular carcinoma (HCC), microvascular invasion (MVI), time intensity curves (TICs), prediction

DOI: 10.3233/CH-201085

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Curta, Adrian | Jaber, Ahmad | Rieber, Johannes | Hetterich, Holger

Article Type: Research Article

Abstract: INTRODUCTION: Endothelial shear stress (ESS) is a local hemodynamic factor that is dependent on vessel geometry and influences the process of atherogenesis. As in vivo measurements of ESS are not possible, it must be calculated using computational fluid dynamics (CFD). In this feasibility study we explore CFD-models generated from coronary CT-angiography (CCTA) using an individualised blood viscosity and a pulsatile flow profile derived from in vivo measurements. MATERIALS AND METHODS: We retrospectively recruited 25 consecutive patients who received a CCTA followed by a coronary angiography including intravascular ultrasound (IVUS) and generated 3D models of the …coronary arteries from the CT-datasets. We then performed CFD-simulations on these models. Hemodynamically non-relevant stenosis were identified in IVUS. They were isolated in the CFD-model and separated longitudinally into a half with atherosclerotic lesion (AL) and one without (NAL). ESS was measured and compared for both halves. RESULTS: After excluding vessels with no IVUS data or relevant stenosis we isolated 31 hemodynamically non-relevant excentric AL from a total of 14 vessels. AL segments showed consistently significantly lower ESS when compared to their corresponding NAL segments when regarding minimum (0.9 Pa, CI [0.6, 1.2] vs. 1.3 Pa, CI [0.9, 1.8]; p  = 0.004), mean (5.0 Pa, CI [3.4, 6.0] vs. 6.7 Pa, CI [5.5, 8.4]; p  = 0.008) and maximum ESS values (12.4 Pa, CI [8.6, 14.6] vs. 19.6 Pa, CI [12.4, 21.0]; p  = 0.005). Qualitatively ESS was lower on the inside of bifurcations and curvatures. CONCLUSION: CFD simulations of coronary arteries from CCTA with an individualised flow profile and blood viscosity are feasible and could provide further prognostic information and a better risk stratification in coronary artery disease. Further prospective studies are needed to investigate this claim. Show more

Keywords: Coronary artery disease, endothelial shear stress, computational flow dynamics, pulsatile flow, coronary computed tomography, hemodynamics

DOI: 10.3233/CH-201025

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

Authors: de Souza, Maria das Graças C. | Cyrino, Fatima Z. G. A. | Sicuro, Fernando L. | Bouskela, Eliete

Article Type: Research Article

Abstract: BACKGROUND: Protective effects of Ruscus extract on macromolecular permeability depend on its capacity to stimulate muscarinic receptors on endothelial cells and induce the release of endothelium derived relaxing factors (EDRFs). OBJECTIVE: To investigate if these effects depend only on activation of muscarinic receptors or EDRFs release are also necessary. We have also investigated the participation of Ruscus extract on muscarinic-induced release of EDRFs on microvascular diameters. METHODS: Hamsters were treated daily during two weeks with Ruscus extract (50, 150 and 450 mg/kg/day) and then macromolecular permeability induced by histamine and arteriolar …and venular diameters after cyclooxygenase (COX) and nitric oxide synthase (NOS) inhibitors: indomethacin and Nω-Nitro-L-arginine (LNA), respectively applied topically at 10–8 M, 10–6 M and 10–4 M were observed on the cheek pouch preparation. RESULTS: Ruscus extract decreased macromolecular permeability in a dose-dependent fashion and did not affect microvascular diameters. NOS and COX inhibitors enhanced this effect. NOS inhibition reduced arteriolar diameter and COX blocking decreased arteriolar and venular diameters at the lowest dose and increased them at higher doses of Ruscus extract. CONCLUSION: The protective effect of Ruscus extract on macromolecular permeability seems to be mediated only via muscarinic receptors. Muscarinic activation attenuated vasoconstrictive tone through cyclooxygenase-independent endothelium derived relaxing factors. Show more

Keywords: Ruscus extract, muscarinic receptors, endothelium derived relaxing factors, macromolecular permeability, microvascular diameter, cyclooxygenase, nitric oxide synthase, hamster cheek pouch preparation

DOI: 10.3233/CH-201019

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-17, 2021

Authors: White, Jennell | Moira, Lancelot | Gao, Xiufeng | Tarasev, Michael | Chakraborty, Sumita | Emanuele, Marty | Hines, Patrick C.

Article Type: Research Article

Abstract: BACKGROUND: Red blood cell (RBC)-modifying therapies have provided new opportunities for patients with sickle cell disease, although the absence of validated biomarkers of RBC function is a barrier to FDA approval and clinical adoption. Flow Adhesion (FA) and Mechanical Fragility (MF) biomarkers objectively stratify individuals with SCD into pro-adhesive vs pro-hemolytic phenotypes respectively, which may potentially help predict therapeutic responses. OBJECTIVE: A Phase 3 clinical trial to determine the effectiveness of vepoloxamer, an RBC-modifying therapy in sickle cell disease (SCD), failed to meet its primary clinical outcome. The aim of this study was to determine whether standardized flow …adhesion and mechanical fragility bioassays could differentiate cellular level “responders” from “non-responders” to vepoloxamer treatment. METHODS: Standardized biomarkers of RBC function (adhesion and mechanical fragility) were utilized in this study to assess the effect of veploxamer on blood samples collected from SCD subjects and to determine whether our assays could differentiate cellular-level “responders” from “non-responders” to vepoloxamer treatment. A Wilcoxon signed-rank test was used to test for differences in adhesion in response to varying vepoloxamer treatments and a Wilcoxon Mann-Whitney test was used to assess differences in mechanical fragility, pre- and post-vepoloxamer treatment. A p -value<0.05 was considered significant. RESULTS: In this study, we report that in vitro treatment with vepoloxamer reduced adhesion by >75%in 54%of patient samples and induced changes in the membranes of sickle erythrocytes (SSRBCs) making sickle cells behave more like normal erythrocytes (AARBCs) in terms of their resistance to hemolysis. CONCLUSION: This study demonstrates that the standardized flow adhesion and mechanical fragility biomarkers described here may be useful tools to predict clinical responders to RBC-modifying therapies. Show more

Keywords: Sickle cell disease, adhesion, vepoloxamer, mechanical fragility, blood function assays

DOI: 10.3233/CH-200944

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Sohn, Sung-Hwa | Kim, Tae Sik | Kim, Ji-Won | Yoo, Sung Mook | Jo, Won-Min

Article Type: Research Article

Abstract: BACKGROUND: Although the number of vascular surgeries performed is increasing, the incidence of complications associated with this surgery has not improved and re-operations are frequently required. Thrombosis in a vessel is the most hazardous postoperative complication. OBJECTIVE: The aim of this study was to evaluate the anti-thrombotic and anti-inflammatory effects of sulodexide compared to aspirin in a rat model. METHODS: We divided the animals into three groups (sham (saline), aspirin, and sulodexide). The abdominal aorta was surgically opened and closed, primarily with 8/0 Prolene sutures. Postoperatively, saline, aspirin, or sulodexide was administered by oral gavage for …14 days to the rats. The degree of neovascularization, thrombus, calcification, inflammatory infiltrates, and fibrosis were analyzed histopathologically by hematoxylin and eosin staining. RESULTS: There was no significant difference in the incidence of postoperative thrombogenesis, but less calcification and inflammatory infiltrates were observed in the sulodexide group compared to the aspirin group. Histopathologic score revealed less infiltration of inflammatory cells and mild calcification for the sulodexide group (0.17±0.41 and 1.33±0.52, respectively) compared to the aspirin group (0.67±0.52 and 1.67±0.52, respectively) at days 14. CONCLUSIONS: This study offers the possibility that sulodexide could be used as an aspirin substitute for the postoperative management of vascular patients, with low gastrointestinal discomfort. In addition, it may also offer reduced postoperative calcification and inflammation. Show more

Keywords: Sulodexide, aspirin, thrombogenesis, calcification, inflammation

DOI: 10.3233/CH-201043

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

Authors: Wang, Zheng-Dong | Li, Hao | Liu, Ming | Li, Ping | Chen, Jian | Liang, Xiang-Wen | Zhu, Xian-Zhang | Liao, Wang

Article Type: Research Article

Abstract: OBJECTIVE: The aim of the present study was to evaluate the effectiveness and safety of nicorandil in improving the area of myocardial infarction in patients with acute myocardial infarction (AMI). METHODS: One hundred and twenty patients with acute ST-segment elevation myocardial infarction (STEMI) admitted to our hospital between December 1, 2018 and December 31, 2019 were selected and randomly allocated to the experimental group (group A, n  = 60) and the control group (group B, n  = 60). In the experimental group, an infusion of nicorandil was given intravenously before the first balloon dilation or 1 minute before the stent …placement, and with the completion of the infusion, nicorandil maintenance infusion was given. In the control group, only balloon dilation and stent placement were undertaken. RESULTS: The postoperative peak levels of myoglobin, creatine kinase isoform and hypersensitive troponin T were significantly lower in group A than in group B (p  <  0.05). Moreover, the left ventricular ejection fraction (LVEF) on the 180th day post operation was substantially greater in group A than in group B (p  <  0.01), and the area of myocardial infarction was significantly smaller in patients in group A than those in group B on the 180th day post operation (p  <  0.01). In terms of the safety, there were no statistically significant differences in the incidence of slow flow/no reflow, malignant arrhythmias, and hypotension within 24 hours post operation between the two groups (p  >  0.05), and no major adverse cardiovascular event (MACE) occurred in either group during the postoperative follow-up period of 180 days (p  >  0.05). CONCLUSION: Intravenous administration of nicorandil in patients with STEMI during the perioperative percutaneous coronary intervention (PCI) period was effective in reducing the area of myocardial infarction and myocardial injury without increasing the incidence of malignant arrhythmias, hypotension, or composite cardiovascular events during the drug administration period. Show more

Keywords: Percutaneous coronary intervention, acute ST-segment elevation myocardial infarction, nicorandil, myocardial infarction area, myocardial injury

DOI: 10.3233/CH-200998

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

Authors: Li, Bao-Hua | Fang, Kuai-Fa | Lin, Pei-Huan | Zhang, Yi-Hui | Huang, Yong-Xiang | Jie, Hai

Article Type: Research Article

Abstract: OBJECTIVE: The aim of the present study was to observe the effect of sacubitril valsartan on cardiac function and vascular endothelial function in patients with chronic heart failure with reduced ejection fraction (HFrEF). METHODS: A total of 80 patients with HFrEF were randomly divided into an observation group and a control group, with 40 patients in each group. Sacubitril valsartan was added to the conventional treatment in the observation group, and perindopril was added to the conventional treatment in the control group. Both groups were treated continuously for 12 weeks. The left ventricular ejection fraction (LVEF), left ventricular …end-diastolic diameter (LVEDD), flow-mediated vasodilatory function (FMD) of the brachial artery, and levels of plasma Ang II, endothelin 1 (ET-1), and calcitonin gene-related peptide (CGRP), together with the serum nitric oxide (NO) and NO synthase (NOS) were compared before and after treatment in the groups. RESULTS: Before the treatment, the levels of LVEF, LVEDD, FMD, Ang II, ET-1, CGRP, NO, and NOS in the observation group were not significantly different from those in the control group (P  >  0.05). However, the levels of LVEF, FMD, CGRP, NO, and NOS in both groups were significantly higher after the treatment than those before the treatment (P  <  0.05) and significantly higher in the observation group than those in the control group. The difference was statistically significant (P  <  0.05). Meanwhile, the levels of LVEDD, Ang II, and ET-1 in both groups decreased significantly after the treatment (P  <  0.05) and were significantly lower in the observation group than those in the control group. The difference was statistically significant (P  <  0.05). CONCLUSION: Sacubitril valsartan might improve endothelial function while increasing cardiac function in HFrEF patients. Show more

Keywords: Sacubitril valsartan, left ventricular ejection fraction, chronic heart failure, cardiac function, endothelial function

DOI: 10.3233/CH-201032

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

Authors: Farber, Paulo L. | Dias, Ana | Freitas, Teresa | Pinho, Ana C. | Viggiano, Diego | Saldanha, Carlota | Silva-Herdade, Ana S.

Article Type: Research Article

Abstract: Background: Calcium, vitamin D and insulin resistance are linked to osteoporosis and cardiovascular disease in menopause. Objective: Determine if hemorheological parameters related to blood viscosity in microcirculation are linked to calcium metabolism and insulin resistance in menopause. Methods: 25-Hydroxyvitamin D (25(OH)D)), 1, 25-dihydroxyvitamin D3 (1, 25(OH)2 D), Parathyroid Hormone, ionized calcium, Glucose, Insulin and Hemoglobin A1c were measured in blood from 43 volunteers. Red blood cells (RBC) aggregation, RBC deformability and Whole Blood Viscosity were also performed. Results: 25(OH)D showed a positive correlation with RBC deformability 0.60 Pa. Subjects with 25(OH)D≤29.00 ng/mL had lower RBC …deformability 0.60 Pa. and higher RBC Aggregation and higher HOMA-IR. Ionized calcium showed a negative correlation with RBC Aggregation. Subjects with ionized calcium ≤1.24 mmol/L showed higher RBC Aggregation. There was a positive correlation between HOMA-IR and RBC Aggregation and HOMA-IR showed a negative correlation with RBC deformability 0.30 Pa. Subjects with HOMA-IR <1.80 showed lower RBC aggregation and higher RBC deformability at 0.30 Pa, 0.60 Pa, 1.20 Pa, 3.0 Pa and 6.0 Pa. Conclusion: Low 25(OH)D, low ionized calcium and high HOMA-IR are related to impaired hemorheology in menopause. RBC aggregation and deformability can be used as biomarkers of calcium metabolism and insulin resistance in menopause. Show more

Keywords: Hemorheology, calcium metabolism, osteoporosis, vitamin D, insulin resistance, cardiovascular diseases

DOI: 10.3233/CH-200956

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2020

Authors: Boisson, Camille | Rab, Minke A.E. | Nader, Elie | Renoux, Céline | van Oirschot, Brigitte A. | Joly, Philippe | Fort, Romain | Stauffer, Emeric | van Beers, Eduard J. | Sheehan, Vivien A. | van Wijk, Richard | Connes, Philippe

Article Type: Research Article

Abstract: Sickle cell disease (SCD) is a genetic disorder characterized by the production of an abnormal hemoglobin (Hb), which, under deoxygenation, may polymerize and cause a mechanical distortion of red blood cell (RBC) into a crescent-like shape. Recently a method, using ektacytometry principle, has been developed to assess RBC deformability as a function of oxygen tension (pO2 ) and is called oxygen gradient ektacytometry (oxygenscan). However, standardization of this test is needed to properly assess the tendency of sickling of RBCs under deoxygenation and to allow comparisons between different laboratories. The study compared the oxygenscan responses during blood storage between distinct …populations of SCD patients. Blood from 40 non-transfused homozygous SCD patients (HbSS), 16 chronically transfused HbSS patients, and 14 individuals with compound heterozygous hemoglobin SC disease (HbSC)at steady-state was collected in EDTA tubes. Measurements were performed within 4 hours after collection and after 24 hours of storage at 4°C. We showed that storage affected the minimum RBC deformability reached during deoxygenation (EImin) in both non-transfused HbSS and HbSC patients and the maximum RBC deformability (EImax) measured before deoxygenation (i.e., in normoxia) in the three groups. In contrast, the tendency of RBCs to sickle under deoxygenation (i.e., the point of sickling; PoS) remained rather stable between the two time of measurements. Collectively, since the time between blood sampling and analysis affects some key oxygen gradient ektacytometry-derived parameters we recommend that each laboratory performs oxygenscan measurements at a standardized time point. Show more

Keywords: Oxygen gradient ektacytometry, sickle cell disease, red blood deformability, storage

DOI: 10.3233/CH-201037

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-4, 2020

Authors: Xiao, Huang | Pengfei, Chen | Fakuan, Tang | Ning, Hua

Article Type: Research Article

Abstract: BACKGROUD: Patients with chest pain and suspected of coronary artery disease(CAD) need further test to confirm the diagnosis. Magnetocardiography (MCG) is a non-invasive and emission-free technology which can detect and measure the weak magnetic fields created by the electrical activity of the heart. OBJECTIVE: This study aimed to investigate the usefulness of the 10 MCG parameters to detect CAD in patients with chest pain by means of a machine learning method of multilayer perceptron(MLP) neural network. METHODS: 209 patients who were suffering from chest pain and suspected of CAD were enrolled in this cross-sectional study. In …all patients, 12-lead electrocardiography(ECG) and MCG test were performed before percutaneous coronary angiography(PCA). 10 MCG parameters were analyzed by MLP neural networks. RESULTS: 11 diagnostic models(M1 to M11) were established after MLP analysis. The accuracies ranged from 71.2% to 90.5%. Two models(M10 and M11) were further analyzed. The accuracy, sensitivity, specificity, PPV, NPV, PLR and NLR were 89.5%, 89.8%, 88.9%, 92.7%, 84.7%, 11.10 and 0.11, of M10, and were 90.0%, 91.4%, 87.7%, 92.1%, 86.6%, 7.43 and 0.10, of M11. CONCLUSIONS: By a method of MLP neural network, MCG is applicable in identifying CAD in patients with chest pain, which seems beneficial for detection of CAD. Show more

Keywords: Magnetocardiography, percutaneous coronary intervention, coronary artery disease, diagnosis, machine learning

DOI: 10.3233/CH-200905

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

Authors: Braune, S. | Bäckemo, J. | Lau, S. | Heuchel, M. | Kratz, K. | Jung, F. | Reinthaler, M. | Lendlein, A.

Article Type: Research Article

Abstract: Nanoporous microparticles prepared from poly(ether imide) (PEI) are discussed as candidate adsorber materials for the removal of uremic toxins during apheresis. Polymers exhibiting such porosity can induce the formation of micro-gas/air pockets when exposed to fluids. Such air presenting material surfaces are reported to induce platelet activation and thrombus formation. Physical or chemical treatments prior to implantation are discussed to reduce the formation of such gas nuclei. Here, we report about the influence of different rewetting procedures – as chemical treatments with solvents – on the thrombogenicity of hydrophobic PEI microparticles and PEI microparticles hydrophilized by covalent attachment of poly(vinyl …pyrrolidone) (PVP) of two different chain lengths. Autoclaved dry PEI particles of all types with a diameter range of 200 – 250 μm and a porosity of about 84% ±2% were either rewetted directly with phosphate buffered saline (24 h) or after immersion in an ethanol-series. Thrombogenicity of the particles was studied in vitro using human sodium citrated whole blood (60 min, 5 rpm vertical rotation). Numbers of non-adherent platelets were quantified, and adhesion of blood cells was qualitatively analyzed by bright field microscopy. Platelet activation (percentage of CD62P positive platelets and amounts of soluble P-Selectin) and platelet function (PFA100 closure times) were analysed. Retention of blood platelets on the particles was similar for all particle types and both rewetting procedures. Non-adherent platelets were less activated after contact with ethanol-treated particles of all types compared to those rewetted with phosphate buffered saline as assessed by a reduced number of CD62P-positive platelets and reduced amounts of secreted P-Selectin (P  < 0.05 each). Interestingly, the hydrophilic surfaces significantly increased the number of activated platelets compared to hydrophobic PEI regardless of the rewetting agent. This suggests that, apart from wettability, other material properties might be more important to regulate platelet activation. PFA100 closure times were reduced and within the reference ranges in the ethanol group, however, significantly increased in the saline group. No substantial difference was detected between the tested surface modifications. In summary, rewetting with ethanol resulted in a reduced thrombogenicity of all studied microparticles regardless of their wettability, most likely resulting from the evacuation of air from the nanoporous particles. Show more

Keywords: Biomaterial, polymer, microparticle, thrombogenicity, hemocompatibility, dynamic in-vitro test, rewetting

DOI: 10.3233/CH-201029

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

Authors: Liu, Qin | Wang, Zhengrong

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the diagnostic value of real-time shear wave elastography (SWE) in children with chronic kidney disease (CKD). METHODS: Children with CKD diagnosed by the ultrasound-guided biopsy between January 2018 and May 2019 were enrolled as the case group. Age- and sex- matched healthy children were selected as the control group. The Young’s Modulus (YM) of the renal cortex was measured by SWE after the traditional ultrasound examination. Variance analysis was performed to compare the values of YM between the two groups. Receiver operating characteristic curve (ROC) analysis was used to compare the values of YM, and …explore the cut-offs of the YM. RESULTS: In the case group (n  = 60, 45% male, mean age of 9.2 years), the kidney YM modulus on the left side (16.8±4.8 kPa vs. 8.3±2.1 kPa) and the right side (16.0±4.7 kPa vs. 8.3±2.4 kPa) were both higher than the control group (all P values <  0.001). With the progress of CKD, the YM value of the left and right kidneys gradually increased. ROC analysis showed that when the left and right kidney YM value was 11.7 kPa and 11.0 kPa, the diagnostic sensitivity and specificity were the highest (left: respectively 93.3% and 95.0%; right: respectively 93.3 % and 91.7%). CONCLUSION: The increase of YM in CKD is related to the progression of renal dysfunction which may provide a new method for early diagnosis of CKD, dynamic monitoring of disease progression, and evaluation of curative effect and prognosis. Show more

Keywords: Shear wave elastography, chronic kidney disease, children

DOI: 10.3233/CH-200982

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

Authors: Krüger-Genge, A. | Tondera, C. | Hauser, S. | Braune, S. | Görs, J. | Roch, T. | Klopfleisch, R. | Neffe, A.T. | Lendlein, A. | Pietzsch, J. | Jung, F.

Article Type: Research Article

Abstract: Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the “Hen’s egg test on chorioallantoic membrane” (HET-CAM) test and a mouse model. The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well …as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants. Show more

Keywords: Gelatin-based hydrogels, immune cells, platelets, in vitro testing, mouse model

DOI: 10.3233/CH-201028

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2020

Authors: Chen, Ji-Xiong | Huang, Xiao-Yan | Wang, Ping | Lin, Wen-Ting | Xu, Wen-Xing | Zeng, Min

Article Type: Research Article

Abstract: This study aimed to investigate the effects of arachidonic acid metabolite epoxyeicosatrienoic acid (EETs) in the apoptosis of endothelial cells induced by tumor necrosis factor-alpha (TNF-α ). After human umbilical vein endothelial cells were cultured, TNF-α /ActD, 14, 15-EET, and HMR-1098 were added, respectively, into the culture medium. The apoptosis level of endothelial cells was detected by flow cytometry. After TNF-α /ActD induced endothelial cell apoptosis, flow cytometry staining showed that endothelial cell apoptosis increased significantly, and the apoptotic cells were significantly reduced after the addition of 14, 15-EET. However, the apoptotic cells significantly increased after the addition of HMR-1098. …Western Blot results showed that the phosphorylation levels of LC3-II and AMPK were increased after TNF-α /ActD induction, and the increase was noticeable after the addition of 14, 15-EET. However, the phosphorylation levels of LC3-II and AMPK significantly decreased after the addition of HMR-1098. The activity of Caspase-8 and -9 decreased significantly after the addition of 14, 15-EET but increased after the addition of HMR-1098. Arachidonic acid can inhibit TNF-α induced endothelial cell apoptosis by upregulating autophagy. Show more

Keywords: Epoxyeicosatrienoic acid, autophagy, apoptosis, endothelial cell, TNF-α

DOI: 10.3233/CH-200946

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

Authors: Zhao, Dan | Shao, Ya-Qin | Hu, Jun | Liu, Dan | Tang, Wei | He, Ning

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the diagnostic value of core-needle biopsy (CNB) guided by contrast-enhanced ultrasound (CEUS) in cervical tuberculous lymphadenitis (CTL). METHODS: 178 patients with pathological confirmation of CTL were retrospectively enrolled. All of them had undergone CNB prior to the final surgery. According to the different ways of puncture guidance, they were divided into two groups: conventional ultrasound (US) group (n  = 81) and CEUS group (n  = 97). The comparison of diagnostic efficacy between two groups was compared and analyzed. RESULTS: Among the 178 patients, 146 were directly diagnosed as CTL by CNB, including 59 patients in …CEUS group and 87 patients in US group. The diagnostic accuracy were 89.7% (87/97) and 72.8% (59/81), respectively (P  <  0.01). For subgroup analyses, differences among diagnostic efficacy ascribed to the different guiding methods were significant in medium size group (>2.0 cm and ≤3.0 cm) and large size group (>3.0 cm), 91.7% for CEUS group vs. 69.0% for US group (P  <  0.05) and 84.4% for CEUS group vs. 57.7% for US group (P  <  0.05), respectively. CONCLUSIONS: In the diagnosis of CTL, compared with the US-guided CNB, CEUS-guided CNB have certain advantages, especially for larger lymph nodes. Show more

Keywords: Contrast-enhanced ultrasound, ultrasound, core-needle biopsy, tuberculous lymphadenitis, cervical

DOI: 10.3233/CH-201038

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

Authors: Jung, Ernst Michael | Engel, Martin | Wiggermann, Philipp | Schicho, Andreas | Lerchbaumer, Markus | Stroszczynski, Christian | Fischer, Thomas | Wiesinger, Isabel

Article Type: Research Article

Abstract: AIM: The aim of this study was to assess the success of irreversible electroporation (IRE) in prostate cancer and to differentiate between reactive changes and tumor. MATERIAL AND METHODS: This is a retrospective pilot study of 50 patients after irreversible electroporation (IRE) in prostate cancer between 50–79 years (mean age 65 years). Each patient received a transabdominal sonography using a 1–6 MHz convex matrix probe. Contrast-enhanced ultrasound (CEUS) was performed after i.v. bolus injection of 2.0 ml sulphur hexafluoride microbubbles. DICOM loops were continuously stored up to one minute. Parametric images were calculated by integrated perfusion analysis software. A …comparison was drawn to a follow-up MRI six months after ablation. RESULTS: While 13 patients showed local recurrence, 37 patients were successfully treated, meaning no local recurrence within six months after ablation. 18 patients showed signs of prostatitis after IRE. Tumorous changes were visually characterized by dynamic early nodular hypervascularization with fast and high wash-in. Correspondingly, nodular red and yellow shades were seen in parametric imaging. All patients with remaining tumor were correctly identified with CEUS and parametric imaging. After IRE there is a relevant decrease in tumor microcirculation in all patients, as seen in more purple shades of the prostate. The sensitivity for detecting residual tumor with CEUS compared to MRI was 76 %, the specificity was 81 %. The corresponding positive predictive value (PPV) was 73 % and the negative predictive value (NPV) was 83 %. CONCLUSION: CEUS and parametric imaging enable a critical analysis of post-ablation defects after IRE for prostate cancer even with a transabdominal approach. Remaining tumor can be detected with the help of pseudo-colors. Show more

Keywords: Parametric imaging, CEUS, prostate cancer, IRE

DOI: 10.3233/CH-201000

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