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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-170298

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

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

Article Type: Research Article

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

Keywords: Ischemia, microcirculation, hemorheology

DOI: 10.3233/CH-170277

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

Authors: Carlisi, Melania | Mancuso, Salvatrice | Lo Presti, Rosalia | Siragusa, Sergio | Caimi, Gregorio

Article Type: Research Article

Abstract: BACKGROUND: in this study, with a re-evaluation of the hemorheological determinants previously described in MGUS subjects and in MM patients, we have detected the calculated whole blood viscosity, according whether to the hematocrit and total plasma protein concentration (de Simone formula) or to the haematocrit and plasma fibrinogen level (Merrill formula), and a marker of the erythrocyte aggregation (albumin/fibrinogen level). METHODS: data were expressed as means±standard deviation. Student’s t test for unpaired data was used to compare MGUS subjects and MM patients. The correlation coefficient between mean erythrocyte aggregation (MEA) and hematocrit (Ht) was evaluated in MGUS, …MM and MGUS + MM groups using the Spearman test. RESULTS: the comparison between MGUS and MM shows that the measured blood viscosity and calculated blood viscosity based on hematocrit and total plasma protein, but not which estimated in relation to the hematocrit and plasma fibrinogen, differentiate the two groups. A difference between the two groups also regards the measured erythrocyte aggregation and its surrogate marker. In addition, the measured plasma viscosity at low shear rate (0.51 s–1 ) and, in particular, the ratio between plasma viscosity at low (0.51 s–1 ) and high (450 s–1 ) shear rates distinguish MGUS and MM. CONCLUSIONS: calculated blood viscosity (de Simone formula and other formulas) and the surrogate marker of erythrocyte aggregation disclose an alike trend with the corresponding hemorheological determinants obtained by using their direct measurement. Show more

Keywords: Calculated whole blood viscosity, measured whole blood viscosity, hematocrit, total plasma protein, albumin, fibrinogen

DOI: 10.3233/CH-211198

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

Authors: Xu, Chen | Wu, Min | Wang, Zhaodong | Liu, Yajun | Zhou, Pinghui | Guan, Jianzhong

Article Type: Research Article

Abstract: BACKGROUND: Application of tranexamic acid (TXA) in the treatment of acetabular fractures could reduce intraoperative and postoperative blood loss. OBJECTIVE: To investigate the effect of single and repeated intravenous infusion of TXA on blood loss of acetabular fractures. METHODS: 120 patients with acetabular fractures admitted to our hospital from January 2017 to September 2020 were retrospectively divided into three groups: Patients accepted 1g TXA at preoperative 30 minutes were defined as single TXA group (n  = 40); Patients accepted 1g TXA at preoperative 30 minutes and 1g TXA at 3 hours after the start of surgery were …defined as repeated TXA group (n  = 40); Patients accepted normal saline at preoperative 30 minutes were defined as control group (n  = 40). RESULTS: The total blood loss in single TXA group and repeated TXA group were significantly lower than control group, and the total blood loss in the repeated TXA group was significantly lower than single TXA group (P  <  0.05). The hidden blood loss from surgery to postoperative 1 day in repeated TXA group was significantly lower than single TXA group and the control group(P  <  0.05). No significant differences were observed in the operative time, postoperative transfusion rate and thrombosis rate among the three groups (P  >  0.05). CONCLUSION: Repeated TXA is more recommended during acetabular fracture surgery since it can reduce the total blood loss without increasing the operative time, postoperative transfusion rate and thrombosis rate compared with single TXA. Show more

Keywords: Tranexamic acid, acetabular fracture, single TXA infusion, repeated TXA infusion, total blood loss, thrombosis rate

DOI: 10.3233/CH-211203

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

Authors: Junqueira, Camillo L. C. | Ferreira, Esmeralci | Junqueira, Adriana S. M. | de Almeida Cyrino, Fatima Zely Garcia | Maranhão, Priscila Alves | Kraemer-Aguiar, Luiz Guilherme | Bottino, Daniel Alexandre | Coelho de Souza, Maria das Graças | Bouskela, Eliete

Article Type: Research Article

Abstract: BACKGROUND: In patients with ischemia and no obstructive coronary artery disease (INOCA), coronary microvascular dysfunction is associated with higher rate of major adverse cardiovascular events. OBJECTIVE: To demonstrate if microvascular dysfunction present in coronary microcirculation of patients with INOCA may be detected noninvasively in their peripheral circulation. METHODS: 25 patients with INOCA and 25 apparently healthy individuals (controls) were subjected to nailfold videocapillaroscopy (NVC) and venous occlusion plethysmography (VOP) to evaluate peripheral microvascular function and blood collection for biomarkers analysis, including soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and C-reactive protein (CRP). RESULTS: …Red blood cell velocity (RBCV) before and after ischemia (RBCVmax ) were significantly lower in patients with INOCA (p  = 0.0001). Time to reach maximal red blood cell velocity (TRBCVmax ) was significantly longer in INOCA group (p  = 0.0004). Concerning VOP, maximal blood flow (p  = 0.004) and its relative increment were significantly lower in patients with INOCA (p  = 0.0004). RBCVmax showed significant correlations with sVCAM-1 (r  = –0.38, p  <  0.05), ET-1 (r  = –0.73, p  <  0.05) and CRP (r  = –0.33, p  <  0.05). Relative increment of maximal post-ischemic blood flow was significantly correlated with sVCAM-1 (r  = –0.42, p  <  0.05) and ET-1 (r  = –0.48, p  <  0.05). CONCLUSIONS: The impairment of microvascular function present in coronary microcirculation of patients with INOCA can be also detected in peripheral microcirculation. Show more

Keywords: Ischemia and no obstructive coronary artery disease, microvascular dysfunction, nailfold videocapillaroscopy, venous occlusion plethysmography

DOI: 10.3233/CH-201065

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

Authors: Pantos, Constantinos | Apostolaki, Vassiliki | Kokkinos, Leonidas | Trikas, Athanassios | Mourouzis, Iordanis

Article Type: Research Article

Abstract: Sepsis and septic shock result in impaired microcirculation and red blood cell rheology which lead to tissue hypoxia and multi-organ failure. Early administration of triiodothyronine prevents tissue hypoxia in experimental sepsis. In this context, a clinical trial was initiated to test the efficacy of acute triiodothyronine administration to combat tissue hypoxia in critically ill COVID19 patients. Here, we provide preliminary data from interim analysis of this study showing a novel acute effect of triiodothyronine on erythrocyte sedimentation rate which may have an important therapeutic impact on red blood cell rheology and tissue hypoxia in sepsis and particular in COVID19 critical …illness. Trial registration: ClinicalTrials.gov, NCT04348513. Registered 16 April 2020, https://clinicaltrials.gov/ct2/show/NCT04348513 Show more

Keywords: Thyroid hormone, hypoxia, erythrocyte sedimentation rate, COVID19, microcirculation, hemorheology

DOI: 10.3233/CH-211215

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-4, 2021

Authors: Jung, E.M. | Dinkel, J. | Verloh, N. | Brandenstein, M. | Stroszczynski, C. | Jung, F. | Rennert, J.

Article Type: Research Article

Abstract: AIM: To evaluate the diagnostic reliability of a new generation wireless point-of care ultrasound device for abdominal and thoracic findings. MATERIAL AND METHODS: 40 patients (16 females, 24 males 19 –80 years, on average 56.1 years) were scanned by an experienced examiner using the new wireless Vscan Air device for abdominal and thoracic findings. The probe frequencies were 2–5 MHz (convex probe) and 3–12 MHz for the linear probe. As a reference standard, all patients were also examined using high-end ultrasound (LOGIQ E9/10). Results were interpreted independently by two examiners in consensus, also with regard to the image quality (0–4, …from not assessable = 0, to excellent 4). RESULTS: In all 40 patients (100%) examination with conventional high-end ultrasound and the Vscan Air ultrasound device was feasible. Sensitivity, specificity, positive and negative predictive value for the diagnosis of abdominal and thoracic findings were 63.3%, 100%, 100%, and 40%, respectively. Most main diagnostic findings were detected using the mobile device compared to the high-end ultrasound. Limitations were found regarding characterization and classification of hepatic and renal tumorous lesions. Image quality revealed mostly minor diagnostic limitations for the mobile device, mean 2.9 (SD –0.300) and was excellent or with only minor diagnostic limitations for conventional high-end ultrasound, mean 3.25 (SD –0.438). CONCLUSION: Due to its easy application and its high diagnostic reliability, point-of-care ultrasound systems of the latest generation represent a valuable imaging method for the primary assessment of abdominal and thoracic findings, especially in patients on intensive care units or in emergency situations. Show more

Keywords: Point-of-care ultrasound, Vscan Air, high-end ultrasound

DOI: 10.3233/CH-211197

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

Authors: Peschel, G. | Grimm, J. | Buechler, C. | Gunckel, M. | Pollinger, K. | Aschenbrenner, E. | Kammerer, S. | Jung, E.M. | Haimerl, M. | Werner, J. | Müller, M. | Weigand, K.

Article Type: Research Article

Abstract: BACKGROUND: A rapid decline of liver stiffness (LS) was detected by non-invasive methods in patients with chronic hepatitis C (HCV) infection during treatment with direct-acting antivirals (DAA). OBJECTIVE: To investigate the influence of inflammation on LS. METHODS: We prospectively examined LS by sonographic shear-wave elastography in 217 patients during DAA therapy from treatment initiation (BL) to 12 weeks after end of therapy (SVR12). Demographic data, laboratory findings and serum levels of cytokines were determined. RESULTS: Values of LS decreased from 1.86 m/s to 1.68 m/s (p  = 0.01) which was most pronounced in patients who had F4 …fibrosis at BL (3.27 m/s to 2.37 m/s; p  <  0.001). Initially elevated values of aminotransferases, ferritin, IgG (p  <  0.001 each) and international normalized ratio (p  <  0.003) declined, thrombocyte count (p  = 0.007) increased. Correlations of these laboratory parameters with BL levels of LS measurement (LSM) were most apparent in patients with F1-F3 fibrosis. Tumor necrosis factor (TNF)-α (p  = 0.031), interleukin (IL)-10 (p  = 0.005) and interferon y inducible protein (IP)-10 (p  <  0.001) decreased in parallel with LSM under DAA therapy and corelated with BL values. CONCLUSION: Decrease of systemic inflammatory parameters correlated with LSM under DAA therapy. We conclude that regression of LSM is attributable to the decline of inflammation rather than reflecting fibrosis. Show more

Keywords: HCV, shear-wave elastography, inflammation, fibrosis

DOI: 10.3233/CH-211193

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2021

Authors: Zhu, Jing-E. | Zhang, Hui-Li | Xu, Hui-Xiong | Yu, Song-Yuan

Article Type: Research Article

Abstract: Hyperthyroidism is a common disease mainly manifested by hyperexcitability of multiple systems and hypermetabolism. Currently, antithyroid drugs (ATDs), radioiodine therapy (RIT), and surgery are mainly used in the clinical treatment for primary hyperthyroidism. We reported a case of a 28-year-old female who received a novel treatment for primary hyperthyroidism. This patient had poor control of thyroid function while taking ATD, and her oral Methimazole (MMI) dose varied repeatedly between 20 mg qd and 15 mg qd, failing to maintain a stable status. To minimize the possible complication and to achieve drug reduction or withdrawal, she refused RIT and surgery and showed up …in our department. The patient, diagnosed with Graves’ disease (GD) and met the surgical indication after systematic clinical evaluation, was subject to ultrasound-guided percutaneous microwave ablation (MWA) of the partial thyroid gland with continuous oral administration of 20 mg qd MMI. The post-ablation condition was stable and the patient was discharged 2 days after the operation. Thyroid ultrasound and serum thyroid function test were examined regularly after ablation and the MMI dosage was gradually reduced according to the results of the biochemical examination. Five weeks after the operation, the patient completely discontinued the medication. Ultrasound-guided percutaneous microwave ablation is minimally invasive, safe, and effective, and has potential to be an alternative treatment besides the 3 classical treatments of hyperthyroidism. Show more

DOI: 10.3233/CH-211180

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

Authors: Kim, Yun-Hee | Choi, Sung-Uk | Youn, Jung-Min | Cha, Seung-Ha | Shin, Hyeon-Ju | Ko, Eun-Ji | Lim, Choon-Hak

Article Type: Research Article

Abstract: BACKGROUND: The prevention of rheologic alterations in erythrocytes may be important for reducing sepsis-associated morbidity and mortality. Remote ischemic preconditioning (RIPC) has been shown to prevent tissue damage caused by severe ischemia and mortality resulting from sepsis. However, the effect of RIPC on erythrocytes in sepsis is yet to be determined. OBJECTIVE: To investigate the effect of RIPC on rheologic alterations in erythrocytes in sepsis. METHODS: Thirty male Sprague-Dawley rats were used in this study. An endotoxin-induced sepsis model was established by intraperitoneally injecting 20 mg/kg LPS (LPS group). RIPC was induced in the right hind limb …using a tourniquet, with three 10-minute of ischemia and 10 min of reperfusion cycles immediately before the injection of LPS (RIPC/LPS group) or phosphate-buffered saline (RIPC group). The aggregation index (AI), time to half-maximal aggregation (T1/2), and maximal elongation index (EImax ) of the erythrocytes were measured 8 h after injection. RESULTS: The AI, T1/2, and EImax values in the LPS and RIPC/LPS groups differed significantly from those in the RIPC group, but there were no differences between the values in the LPS and RIPC/LPS groups. CONCLUSIONS: RIPC did not prevent rheologic alterations in erythrocytes in the rat model of LPS-induced endotoxemia. Show more

Keywords: Rat, red blood cell aggregation, red blood cell deformability, sepsis

DOI: 10.3233/CH-201084

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

Authors: Anžej Doma, Saša | Kristan, Aleša | Debeljak, Nataša | Preložnik Zupan, Irena

Article Type: Research Article

Abstract: Congenital erythrocytosis (CE) is an extremely rare disease and an infrequent cause of heamoglobin and haematocrit elevation. Genetic testing of CE is not widely available. Patients in whom a cause of erythrocytosis is not identified are classified as idiopathic erythrocytosis (IE) patients. In some types of CE thrombotic events have been reported but there is little hard evidence to advise on management in asymptomatic patients. Similarly is true for patients with IE. We describe a young patient who suffered several thromboembolic complications before the diagnosis of CE type 4 was established.

Keywords: Congenital erythrocytosis, idiopathic erythrocytosis, thrombosis, DNA sequencing

DOI: 10.3233/CH-211120

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-5, 2021

Authors: Yang, Yanping | Mao, Wenkai | Wang, Liming | Lu, Lin | Pang, Yunfeng

Article Type: Research Article

Abstract: Atherosclerosis is a major cause of cardiovascular disease, in which vascular smooth muscle cells (VSMCs) proliferation and migration play a vital role. Circular RNAs (circRNAs) have been reported to be correlated with the VSMCs function. Therefore, this study is designed to explore the role and mechanism of circRNA lipase maturation factor 1 (circLMF1) in Human aortic VSMCs (HASMCs). The microarray was used for detecting the expression of circLMF1 in proliferative and quiescent HASMCs. Levels of circLMF1, microRNA-125a-3p (miR-125a-3p), vascular endothelial growth factor A (VEGFA), and fibroblast growth factor 1 (FGF1) were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell …viability, cell cycle progression, and migration were assessed by Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, and transwell assays, respectively. Western blot assay determined proliferating cell nuclear antigen (PCNA), Cyclin D1, matrix metalloproteinase (MMP2), osteopontin (OPN), VEGFA, and FGF1 protein levels. The possible interactions between miR-125a-3p and circLMF1, and miR-125a-3p and VEGFA or FGF1 were predicted by circbank or targetscan, and then verified by a dual-luciferase reporter, RNA Immunoprecipitation (RIP), RNA pull-down assays. CircLMF1, VEGFA, and FGF1 were increased, and miR-125a-3p was decreased in platelet-derived growth factor-BB (PDGF-BB)-inducted HASMCs. Functionally, circLMF1 knockdown hindered cell viability, cell cycle progression, and migration in PDGF-BB-treated HASMCs. Mechanically, circLMF1 could regulate VEGFA or FGF1 expression through sponging miR-125a-3p. Our findings revealed that circLMF1 deficiency could inhibit cell viability, cell cycle progression, and migration of PDGF-BB stimulated atherosclerosis model partly through the miR-125a-3p/VEGFA or FGF1 axis, suggesting that targeting circLMF1 can be a feasible therapeutic strategy for atherosclerosis. Show more

Keywords: CircLMF1, miR-125a-3p, VEGFA, FGF1, human aortic smooth muscle cells

DOI: 10.3233/CH-211166

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

Authors: Fornal, Maria | Lekki, Janusz | Królczyk, Jarosław | Wizner, Barbara | Grodzicki, Tomasz

Article Type: Research Article

Abstract: OBJECTIVE: The study aims at assessing the relationship between blood pressure, heart geometry parameters, and the erythrocyte content of sulfur, potassium, chlorine and phosphorus, in a group of patients with laboratory systolic and diastolic blood pressure (SBP, DBP) below 140 or 90 mm Hg, respectively, who were otherwise healthy and untreated. METHODS: The study group consisted of 42 adults recruited in a primary care setting. The individuals were healthy, not undergoing any therapy and free from smoking. For each individual, data were obtained on: average 24-hour SBP and DBP, left ventricle geometry, complete blood count, lipids profile, fibrinogen, hs-CRP …and the erythrocyte concentration of sulfur (S), potassium (K), chlorine (Cl) and phosphorus (P). RESULTS: Multivariate regression analysis showed statistically significant relationships of diastolic posterior wall thickness (PWTd) and relative wall thickness (RWT) with the concentration ratio of sulfur and potassium (S/K) in erythrocytes: PWTd and RWT increase as the S/K ratio increases. Also, SBP was found to be positively correlated with the S/K ratio. CONCLUSIONS: The increase in sulfur content in RBCs could be an indicator of the downregulation of nitric oxide (NO) erythrocyte bioavailability exerted by endogenously produced hydrogen sulfide (H2 S), and, in consequence, a marker of the development of hypertension and/or adverse changes in heart geometry. Show more

Keywords: Blood pressure measurement/monitoring, heart geometry, elemental sulfur content of erythrocytes, microelement concentration in erythrocytes

DOI: 10.3233/CH-211117

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

Authors: Arihan, Okan | Nader, Elie | Oto, Gokhan | Kocak, Yilmaz | Fort, Romain | Connes, Philippe

Article Type: Research Article

Abstract: Sickle cell anemia (SCA) is a genetic disorder characterized by chronic hemolysis and the presence of erythrocytes with low deformability, which may trigger vaso-occlusive crises. We tested the in-vitro effects of aqueous extract of vhives (Allium schoenoprasum L.) on erythrocyte deformability of SCA patients. Blood samples from 6 apparently healthy volunteers and 5 SCA patients were collected into heparin coated tubes. Both apparently healthy and SCA patient blood samples were incubated with 80μg/mL chives plant aqueous extract at 37°C for 60 min and erythrocyte deformability was measured by ektacytometry (3 Pa and 30 Pa; 37°C). Results of incubation …of apparently healthy blood samples with plant extract showed that incubation did not alter erythrocyte deformability significantly. However, for SCA blood samples, erythrocyte deformability decreased significantly with plant extract exposure at 3 Pa (p  <  0.043) and 30 Pa (p  <  0.043). In conclusion, although ex-vivo incubation with plant extract does not fully model gastrointestinal processing of onions, the decrease in SCA erythrocyte deformability following incubation with aqueous chives should stimulate further studies to test the in-vivo effects of this diet in sickle cell mice. Show more

Keywords: Chives, allium, erythrocyte deformability, ektacytometry, sickle cell anemia

DOI: 10.3233/CH-201036

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-5, 2021

Authors: Zhao, Yanan | Jiang, Tao | Lv, Kun | Pan, Minqiang | Wen, Qing | Huang, Pintong

Article Type: Research Article

Abstract: BACKGROUND: The aim was to retrospectively analyze the ultrasonographic and clinical characteristics of focal inflammatory masses and malignant masses of salivary gland by using B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) for differential analysis. METHODS: The features of US and CEUS were retrospectively analyzed for 19 cases of focal salivary inflammatory masses and 45 cases of malignant salivary masses. All cases were confirmed by pathohistological examination. RESULTS: On B-mode US, the incidence of expansive growth patterns of malignant salivary masses (44.4%, 20/45) was significantly higher than that of focal salivary inflammatory masses (15.8%, 3/19) (p  = 0.029). …The rate of lymphadenopathy surrounding salivary glands of malignant salivary masses (42.2%, 19/45) was significantly higher than that of focal salivary inflammatory masses (15.8%, 3/19) (p  = 0.042). On CEUS, clear enhancement margins were more common in malignant salivary masses (44.4%, 20/45) compared to focal salivary inflammatory masses (15.8%, 3/19) (p  = 0.029); Rapid washout was more common in malignant salivary masses (82.2%, 37/45) than focal salivary inflammatory masses (31.6%, 6/19) (p  <  0.001). Rapid washout on CEUS and craniocaudal diameter were independent predictive factors in differentiating salivary inflammatory masses and malignant masses according to binary logistic regression analysis. US and CEUS achieved a sensitivity of 80.0%, a specificity of 78.9%and an accuracy of 80.0%for discrimination between salivary inflammatory masses and malignant masses. CONCLUSION: Therefore, a multimodal ultrasonographic pathway combining clinical manifestations, B-mode US and CEUS was needed to differentiate between salivary focal inflammatory masses and malignancies to avoid unnecessary biopsies. Show more

Keywords: Chronic sialadenitis, salivary mass, ultrasound (US), contrast-enhanced ultrasound (CEUS)

DOI: 10.3233/CH-211151

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

Authors: Wang, Peihua | Nie, Fang | Dong, Tiantian | Wang, Guojuan | Wang, Lan | Fan, Xiao

Article Type: Research Article

Abstract: OBJECTIVE: To explore the correlation between two-dimensional ultrasound (2D-US), contrast-enhanced ultrasound (CEUS) and microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 56 patients with surgically pathologically confirmed HCC lesions were included. Patients were classified according to the presence of MVI: MVI positive group (n  = 17) and MVI negative group (n  = 39). 2D-US and CEUS examinations were performed within two weeks before surgery. The 2D-US and CEUS features were analyzed for correlation with MVI. Statistically significant parameters of ultrasound characteristic were scored, and the results of the scores were analyzed by ROC curve. …RESULTS: There were statistically significant differences in tumor shape, boundary, capsule, CEUS portal phase and delayed phase enhancement pattern, time to wash out, and tumor margin after enhancement (P  <  0.05), while there were no statistically significant differences in tumor location and size, CEUS arterial phase enhancement pattern, initial time, time to peak, and peritumor enhancement (P  >  0.05). When diagnosing the presence of MVI in HCC patients with cut-off value of the score combined 2D-US and CEUS features≥3, the maximum Jorden index was 0.58, and its diagnostic sensitivity and specificity were 94.10%and 64.1%, respectively, meaning that the total score≥3 was highly suspicious of the presence of MVI. CONCLUSIONS: 2D-US and CEUS are feasible methods for preoperative prediction of MVI in HCC, and can provide some theoretical basis for individualized clinical treatment. Show more

Keywords: Hepatocellular carcinoma (HCC), microvascular invasion (MVI), contrast-enhanced ultrasound (CEUS)

DOI: 10.3233/CH-211190

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

Authors: Krasulina, K.A. | Glazkova, P.A. | Glazkov, A.A. | Kulikov, D.A. | Rogatkin, D.A. | Kovaleva, Y.A. | Bardeeva, J.N. | Dreval, A.V.

Article Type: Research Article

Abstract: BACKGROUND: Neurogenic regulation is involved in the development of microcirculation response to local heating. We suggest that microvascular reactivity can be used to estimate the severity of diabetic polyneuropathy (DPN). OBJECTIVE: To evaluate the prospects for using the parameters of skin microvascular reactivity to determine the severity of DPN. METHODS: 26 patients with diabetes mellitus were included in the study (patients with retinopathy (n  = 15), and without retinopathy (n  = 11)). The severity of DPN was assessed using Michigan Neuropathy Screening Instrument (MNSI) and Norfolk QOL-DN (NQOLDN). Skin microcirculation was measured by laser Doppler flowmetry with local …heating test. RESULTS: There were revealed moderate negative correlations between microvascular reactivity and the severity of DPN (for MNSI (Rs = –0.430), for NQOLDN (Rs = –0.396)). In patients with retinopathy, correlations were stronger than in the general group (for MNSI (Rs = –0.770) and NQOLDN (Rs = –0.636)). No such correlations were found in patients without retinopathy. CONCLUSION: Correlation of the microvascular reactivity and DPN was revealed in patients with registered structural disorders in microvessels (retinopathy). The lack of such correlation in patients without retinopathy may be explained by the intact compensatory mechanisms of microvessels without severe disorders. Show more

Keywords: Diabetes mellitus, diabetic neuropathies, microcirculation, skin, laser-Doppler flowmetry, diabetic retinopathy

DOI: 10.3233/CH-211177

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

Authors: Rother, Ulrich | Theune, Mona | Lang, Werner | Meyer, Alexander

Article Type: Research Article

Abstract: BACKGROUND: Negative pressure wound therapy (NPWT) has been established over years for treatment of chronic and complex wounds. OBJECTIVE: Aim of this study was to investigate the effect NPWT on the microperfusion. METHODS: Prospective single centre analysis of patients treated with NPWT due to acute (ACUTE) wounds after fasciotomy or patients with chronic wounds (CHRONIC) due to a chronic limb threatening ischemia was performed. NPWT was conducted through a three days sequence with a negative pressure of –120 mmHg. Before after and during the entire period of therapy the microperfusion was assessed (O2C™, LEA Medizintechnik). …RESULTS: Comparison of the perfusion values of 28 patients (CHRONIC/ACUTE 5/23, women/men 8/20) before and after the NPWT sequence showed a non-significant improvement in the CHRONIC group (supine position: p  = 0.144, elevated position p  = 0.068) and a significant decrease in the ACUTE group (supine position p  = 0.012, elevated position p  = 0.034). This effect could also been demonstrated during the NPWT over time (CHRONIC: supine position: p  = 0.320, elevated position: p  = 0.053, ACUTE: supine position: p  = 0.021, elevated position: p  = 0.012). CONCLUSION: Microperfusion measurements showed alterations and differences in wound bed perfusion of acute and chronic wounds; acute wounds tended to a decrease of blood flow, whereas this effect was not seen in chronic wounds in peripheral artery disease. Show more

Keywords: Negative pressure therapy, microperfusion, CLTI, fasciotomy, O2C

DOI: 10.3233/CH-211189

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

Authors: Piao, Jinxiang | Yoo, Chaeyoung | Kim, SeonYoung | Whang, Youn-Wha | Choi, Cheol Ung | Shin, Sehyun

Article Type: Research Article

Abstract: BACKGROUND: Assessment of platelet inhibition for aspirin therapy is important to manage patients who are at potential risk of developing thrombotic and hemorrhagic complications. OBJECTIVE: This study aimed to evaluate a new platelet assay (Anysis-Aspirin), compare it with VerifyNow-Aspirin in patients with cardiac diseases, and analyze the aspirin resistance rates between the two devices. METHODS: Citrated blood samples were collected from patients with cardiac diseases referred for the aspirin response test. In the Anysis assay, a test result was provided with a blood flow migration distance (MD) until blood flow stoppage, which was comparable to aspirin …reaction units (ARUs) obtained using VerifyNow. The measurements were simultaneously conducted using the two devices and compared. RESULTS: The MD without and with aspirin use was 160±33 and 254±23 mm, respectively (p  <  0.0001). Compared with VerifyNow (reference), the sensitivity and specificity of Anysis-200 were 96.3 and 90.3%, respectively (area under the curve, 0.968). Furthermore, the aspirin resistance rate in aspirin-administered patients was 20.9%using VerifyNow and 16.5%for Anysis-200. The Cohen’s kappa coefficient between the two devices was 0.81, indicating an almost perfect agreement between the two devices. CONCLUSIONS: Anysis-Aspirin, a novel aspirin assay for assessing platelet inhibition, showed excellent agreement with VerifyNow-Aspirin with high accuracy and precision. The Anysis-aspirin assay would be used as a point-of-care test to assess aspirin non-responsiveness and abnormal platelet reactivity. Show more

Keywords: Platelet function, aspirin, Anysis-200 analyzer, VerifyNow

DOI: 10.3233/CH-211171

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

Authors: Buono, Michael | Rostomily, Kaitlyn

Article Type: Research Article

Abstract: BACKGROUND: It has previously been reported that chronic hypoxia increases blood viscosity. The increase is usually attributed to polycythemia-induced increases in hematocrit. However, the effect of acute hypoxia in humans on blood viscosity is unknown. OBJECTIVE: Therefore, the purpose of this study was to determine the effect of acute hypoxia, independent of changes in hematocrit, on blood and plasma viscosity. METHODS: Nine healthy volunteers breathed room air for 30 min, followed by 30 min of breathing 15% oxygen. Blood samples were collected at the end of both the normoxic and hypoxic conditions. Blood viscosity, plasma viscosity, and hematocrit …were measured in each sample. RESULTS: The mean±SD hemoglobin oxygen saturation significantly (P  <  0.05) decreased from 98±1% during normoxia to 87±2% during hypoxia. Hematocrit was essentially identical for the two conditions (42.1% vs. 42.0%). Blood viscosity was not significantly different for the two conditions with a mean of 2.89±0.17 cP during normoxia and 2.83±0.19 cP during hypoxia. Likewise, plasma viscosity was not significantly different for the two conditions with a mean of 1.19±0.04 cP during normoxia and 1.19±0.05 cP during hypoxia. CONCLUSION: Such results suggest that acute normobaric hypoxia, independent of changes in hematocrit, does not increase blood or plasma viscosity. Show more

Keywords: Blood viscosity, hypoxemia, hypoxia, hematocrit

DOI: 10.3233/CH-211125

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-4, 2021

Authors: Sun, Ying-Hua | Yuan, Lin | Du, Yang | Zhou, Jian-Guo | Lin, Sam Bill | Zhang, Rong | Dong, Yi | Chen, Chao

Article Type: Research Article

Abstract: BACKGROUND: Lung ultrasound (LUS) is a bedside technique that can be used on diagnosis and follow-up of neonatal respiratory diseases. However, there are rare reports on the ultrasound features of bronchopulmonary dysplasia (BPD) which is one of the most common chronic lung diseases in preterm infants. OBJECTIVE: To describe the ultrasound features of different BPD levels, and to investigate the value of ultrasound in evaluating moderate-to-severe BPD. METHODS: In this prospective cohort study, newborns of less than 37 weeks’ gestational age in neonatal intensive care unit (NICU) were included. The LUS characteristics including pleural line, alveolar-interstitial …syndrome (AIS), retrodiaphragmatic hyperechogenicity and diaphragmatic morphology were observed and recorded. The reliability of LUS in evaluating moderate and severe BPD were compared and calculated. RESULTS: A total of 108 infants were enrolled in our study: 39, 24, 29, 16 infants had non, mild, moderate and severe BPD. The median(IQR) pleura thickness in the moderate-to-severe BPD group was 1.7(1.6–1.85) mm, which was thicker than that in the none-to-mild BPD infants (P  <  0.001), meanwhile the proportions of rough pleural lines, diffuse AIS, retrodiaphragmatic hyperechogenicity, small cysts above the diaphragm and rough diaphragm in the moderate-to-severe BPD group were also higher than those in none-to-mild BPD group (86.7% vs 36.5, 57.8% vs 7.9%, 37.8% vs 0, 33.3% vs 0, P  <  0.001). In evaluating moderate-to-severe BPD, rough pleura had 91.1% (95% confidence interval [CI]: 0.793–0.965) in sensitivity, 91.3% (95% CI: 0.797–0.966) in negative predictive value (NPV), and 66.7% (95% CI: 0.544–0.771) in specificity. Small cysts had 100% (95% CI: 0.941-1) in specificity, 100% (95% CI: 0.816-1) in PPV, and 37.8% in sensitivity (95% CI: 0.251–0.524). Rough diaphragm had 100% (95% CI: 0.943-1) in sensitivity, 100% (95% CI: 0.796-1) in PPV and 33.3% (95% CI: 0.211–0.478) in specificity. CONCLUSIONS: Depending on its unique advantages such as convenient, no radiation and repeatable, LUS is a valuable imaging method in assessing the severity of BPD, especially in moderate and severe BPD. Show more

Keywords: Bronchopulmonary dysplasia, lung, preterm infants, ultrasound

DOI: 10.3233/CH-211132

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

Authors: Chen, Yanling | Wang, Wenping

Article Type: Research Article

Abstract: AIM: To explore the diagnostic ability of contrast-enhanced ultrasound (CEUS) in distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for studies reporting the diagnostic accuracy of CEUS in differentiating ICC from HCC. The diagnostic ability of CEUS was assessed based on the pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the curve (AUC) with 95% confidence intervals (CIs). The methodologic quality was assessed by the QUADAS-2 tool. Subgroup analyses, meta-regression and investigation of publication …bias were performed to identify the source of heterogeneity. RESULTS: A total of eight studies were included, consisting of 1,116 patients with HCC and 529 with ICC. The general diagnostic performance of CEUS in distinguishing ICC and HCC were as follows: pooled sensitivity, 0.92 (95% CI: 0.84–0.96); pooled specificity, 0.87 (95% CI: 0.79–0.92); pooled PLR, 7.1 (95% CI: 4.1–12.0); pooled NLR, 0.09 (95% CI: 0.05–0.19); pooled DOR, 76 (95% CI: 26–220) and AUC, 0.95(95% CI: 0.93–0.97). Different liver background may be a potential factor that influenced the diagnostic accuracy of CEUS according to the subgroup analysis, with the pooled DOR of 89.67 in the mixed liver background group and 46.87 in the cirrhosis group, respectively. Six informative CEUS features that may help differentiate HCC from ICC were extracted. The three CEUS features favoring HCC were arterial phase hyperenhancement(APHE), mild washout and late washout (>60s); the three CEUS favoring ICC were arterial rim enhancement, marked washout and early washout(<60s). No potential publication bias was observed. CONCLUSION: CEUS showed great diagnostic ability in differentiating ICC from HCC, which may be promising for noninvasive evaluation of these diseases. Show more

Keywords: Contrast-enhanced ultrasonography, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, meta-analysis, differentiation

DOI: 10.3233/CH-211145

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

Authors: Telek, Vivien | Erlitz, Luca | Caleb, Ibitamuno | Nagy, Tibor | Vecsernyés, Mónika | Balogh, Bálint | Sétáló, György | Hardi, Péter | Jancsó, Gábor | Takács, Ildikó

Article Type: Research Article

Abstract: BACKGROUND: Ischemia-reperfusion injury (IRI) can cause insufficient microcirculation of the transplanted organ and results in a diminished and inferior graft survival rate. OBJECTIVE: This study aimed to investigate the effect of different doses of an anti-diabetic drug, Pioglitazone (Pio), on endoplasmic reticulum stress and histopathological changes, using an in situ perfusion rat model. METHODS: Sixty male Wistar rats were used and were divided into six groups, consisting of the control group, vehicle-treated group and four Pio-treated groups (10, 20, 30 and 40 mg/kg Pio was administered). The rats were perfused through vena cava and an outflow …on the abdominal aorta occurred. Following the experiment, kidneys and livers were collected. The level of the endoplasmic reticulum stress markers (XBP1 and Caspase 12) was analyzed using Western blot and histopathological changes were evaluated. RESULTS: Histopathological findings were correlated with the Western blot results and depict a protective effect corresponding to the elevated dosage of Pioglitazone regarding in situ perfusion rat model. CONCLUSIONS: In our study, Pioglitazone can reduce the endoplasmic reticulum stress, and the most effective dosage proved to be the 40 mg/kg Pio referencing the kidney and liver samples. Show more

Keywords: Endoplasmic reticulum stress, pioglitazone, in situ perfusion, cell damage

DOI: 10.3233/CH-211163

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2021

Authors: Piao, Jinxiang | Yoo, Chaeyoung | Kim, SunYoung | Whang, Youn-Wha | Shin, Sehyun | Choi, Cheol Ung

Article Type: Research Article

Abstract: BACKGROUND: Analyzing responsiveness to P2Y12 therapy is vital to preventing thrombotic and hemorrhagic complications in patients with cardiovascular diseases. OBJECTIVE: This study evaluates a new Anysis-P2Y12 assay system against VerifyNow-P2Y12 in cardiac patients and analyzes the P2Y12 low-response rates of the two devices with various cutoff values. METHODS: In total, 125 citrated blood samples were collected from cardiac patients referred for a P2Y12 antiplatelet response test. In the Anysis assay, the test result was the migration distance (MD) until the blood flow stops, which is comparable to both P2Y12 reaction units and percent inhibition obtained using …VerifyNow. RESULTS: The MDs without and with P2Y12 were 182±30 and 264±12 mm, respectively (p  <  0.0001). Compared to VerifyNow-P2Y12, the sensitivity and specificity of Anysis-200 were 96.8%and 88.7%, respectively. Cohen’s kappa coefficient between the two devices was 0.761, indicating a high agreement. However, there was an apparent difference in the low-response rate to P2Y12, which was 36.5%for VerifyNow and 5.9%for Anysis. CONCLUSIONS: The performance of the newly developed platelet function assay, Anysis-P2Y12 was equivalent to that of VerifyNow-P2Y12 in terms of sensitivity and specificity. The Anysis-P2Y12 assay may help screen patients with abnormal P2Y12 non-responsiveness. Show more

Keywords: Platelet function, antiplatelet, P2Y12, Anysis, VerifyNow

DOI: 10.3233/CH-211104

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

Authors: Zhang, Lei | Li, Qiulai | Chen, Yanxia | Zhu, Qiao

Article Type: Research Article

Abstract: BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) could induce endothelial injury and played a vital role in the progression and development of atherosclerosis. This study aimed to investigate the role of Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in ox-LDL-induced human umbilical vascular endothelial cells (HUVECs) injury and the potential mechanisms. METHODS: Cell proliferation and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry assay, respectively. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were detected by corresponding detection kits, respectively. Quantitative real-time PCR (qRT-PCR) was …conducted to measure the expression of OIP5-AS1 or microRNA-30c-5p (miR-30c-5p) in HUVECs. Binding between OIP5-AS1 and miR-30c-5p was predicted through bioinformatics analysis and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Western blot was used to analyze p-IκB, IκB, p-p65 and p65 levels. RESULTS: In HUVECs, exposure to ox-LDL led to a decrease in cell viability and an increase in LDH release and apoptosis with concomitant enhancement of oxidative stress, as evidenced by increased ROS and MDA generation, as well as decreased SOD activity and NO levels, while OIP5-AS1 knockdown or miR-30c-5p upregulation could rescue these effects above. Mechanically, OIP5-AS1 functioned as a sponge of miR-30c-5p. OIP5-AS1-induced injury and apoptosis, oxidative stress and activation of NF-κB pathway were reversed by miR-30c-5p in ox-LDL-treated HUVECs. CONCLUSION: OIP5-AS1 contributed to ox-LDL-treated HUVECs injury by activation of NF-κB pathway via miR-30c-5p. Show more

Keywords: Atherosclerosis, ox-LDL, OIP5-AS1, miR-30c-5p, NF-κB pathway, endothelial injury, oxidative stress injury

DOI: 10.3233/CH-211130

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

Authors: Zuo, Dongsheng | Yang, Kefeng | Wu, Size

Article Type: Research Article

Abstract: BACKGROUND: The contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) is a relative new algorithm for hepatocellular carcinoma (HCC) assessment. OBJECTIVE: To validate the diagnostic efficiency of the intravascular perfusion based CEUS LI-RADS for HCC. METHODS: Archives of 873 patients with focal liver lesions (FLLs) undergoing CEUS were reviewed, and target images were read by two sonologists independently according to the CEUS LI-RADS. The diagnostic performance was calculated and compared. RESULTS: Assessment with reference to CEUS LI-RADS, 87 of 218 FLLs (39.9%) were categorized as LR-5, 131 of 218 FLLs (60.1%) were …categorized as non-LR-5, 19 of 99 HCCs were categorized as non-LR-5, and 7 of 119 non-HCCs were categorized as LR-5. The sensitivity, specificity, AUROC, positive and negative predictive values of CEUS LI-RADS for diagnosing HCC were 80.81%(95%CI: 71.7%–88.0%), 94.1%(95%CI: 88.3%–97.6%), 0.87 (95%CI: 0.82–0.92), 91.9%(95%CI: 84.1%–96.7%), and 85.5%(95%CI: 78.3%–91.0%), respectively. CONCLUSIONS: The diagnostic efficiency of the intravascular perfusion based CEUS LI-RADS for the evaluation of HCCs is very good. Show more

Keywords: Keywords:

DOI: 10.3233/CH-211164

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

Authors: Caimi, G. | Urso, C. | Brucculeri, S. | Amato, C. | Carlisi, M. | Lo Presti, R.

Article Type: Research Article

Abstract: We present a cohort of 100 subjects [43 men and 57 women; median age 66.00(25) ] who were tested using carotid ultrasound to identify subclinical carotid atherosclerosis (SCA). We have evaluated the behaviour of whole blood viscosity (WBV) at high (450 s–1 ) and low (0.51 s–1 ) shear rates, plasma viscosity (450–1 ), hematocrit and mean erythrocyte aggregation. When compared to normal control subjects, using the Mann-Whitney test, we observed in SCA patients a significant increase in WBV only. The results were substantial after having divided the SCA subjects according to the cardiovascular risk factors (CRFs) and the degree of …insulin resistance; the research was performed using two surrogate indexes such as TG/HDL-C and TyG. With the division carried out according to CRFs, employing the Kruskal-Wallis test, results show a significant increase in WBV (at high and low shear rates), in plasma viscosity, in erythrocyte aggregation and plasma fibrinogen level. Whereas by dividing them into the median of TG/HDL-C and TyG, we noticed a significant increase in WBV (at high and low shear rates) and in erythrocyte aggregation in the two groups with high TG/HDL-C ratio and with high TyG; having found an increased level of plasma fibrinogen in the latter. The data underlines the role of the main hemorheologic aspects in subclinical carotid atherosclerosis being closely correlated to the CRFs and different degrees of insulin resistance. Show more

Keywords: Subclinical carotid atherosclerosis, hemorheological determinants, traditional cardiovascular risk factors, insuline-resistence, uric acid

DOI: 10.3233/CH-211105

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

Authors: Hodis, Howard N. | Mack, Wendy J. | Meiselman, Herbert J. | Kalra, Vijay | Liebman, Howard | Hwang-Levine, Juliana | Dustin, Laurie | Kono, Naoko | Mert, Melissa | Wenby, Rosalinda B. | Huesca, Emiliano | Li, Yanjie | Yan, Mingzhu | St. John, Jan A | Whitfield, Lora

Article Type: Research Article

Abstract: BACKGROUND: Described to be antithrombotic and antihypertensive, nattokinase is consumed for putative cardiovascular benefit. However, no large-scale, long-term cardiovascular study has been conducted with nattokinase supplementation. OBJECTIVE: To determine the effect of nattokinase on subclinical atherosclerosis progression and atherothrombotic biomarkers. METHODS: In this double-blinded trial, 265 individuals of median age 65.3 years, without clinical evidence of cardiovascular disease (CVD) were randomized to oral nattokinase 2,000 fibrinolytic units or matching placebo. Primary outcome was rate of change in subclinical atherosclerosis measured by serial carotid ultrasound every 6 months as carotid artery intima-media thickness (CIMT) and carotid arterial …stiffness (CAS). Additional outcomes determined at least every 6 months were clinical parameters including blood pressure and laboratory measures including metabolic factors, blood rheology parameters, blood coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage cellular activation markers. RESULTS: After median 3 years of randomized treatment, annualized rate of change in CIMT and CAS did not significantly differ between nattokinase supplementation and placebo. Additionally, there was no significant effect of nattokinase supplementation on blood pressure or any laboratory determination. CONCLUSIONS: Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD. Show more

Keywords: Nattokinase, natto, fermented soy, soybeans, fibrinolysis, atherosclerosis, cardiovascular disease, carotid artery intima-media thickness, blood pressure, thrombosis, blood rheology

DOI: 10.3233/CH-211147

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2021

Authors: Astapenko, David | Ticha, Alena | Hyspler, Radomir | Tomasova, Adela | Navratil, Pavel | Maly, Ondrej | Parizkova, Renata Cerna | Cizkova, Dana | Huey, Shin Chua | Lehmann, Christian | Malbrain, Manu L.N.G. | Cerny, Vladimir

Article Type: Research Article

Abstract: BACKGROUND: The endothelial glycocalyx (EG) plays a vital role in the physiology and pathophysiology of human microcirculation. Having relevant EG damage model would be important tool for testing new interventions aiming at EG protection and recovery. We describe the first in vivo EG damage model in pig. OBJECTIVE: To investigate the course of animal EG damage induced by specific enzymes. MATERIAL AND METHODS: Four anesthetized piglets received enzymes: 1g hyaluronidase and 25 IU heparanase I intravenously. Blood and urine samples were collected at baseline and 20/40/60/80/100/120 min for detecting markers of endothelial and EG function. Sublingual …microcirculation and EG thickness were assessed by Side-stream Dark Field (SDF) imaging and Perfused Boundary Region (PBR) respectively. EG of the mesentery artery was visualized in fluorescent microscopy. RESULTS: Biochemical marker of EG damage syndecan-1 showed temporary increase with return to baseline and was reflected by PBR values. Albumin levels suggested brief period of capillary leakage (decrease in the serum, increase in the urine) with a trend to normalization. Urine glycosaminoglycans peaked at 120 minutes. Microcirculatory perfusion parameter showed significant alteration. Diffusion parameters were altered with no statistical significance. CONCLUSION: EG damage induced by specific enzymes was reflected by temporary changes of biochemical makers together with alteration of microcirculation and changes in fluorescent microscopy of EG layer. Our results support to further validate presented model of EG damage on a larger number of animals. Show more

Keywords: Microcirculation, endothelial glycocalyx, hyaluronidase, heparanase, albuminuria

DOI: 10.3233/CH-211133

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

Authors: Li, Jia-Xin | Zhang, Hui-Li | Xu, Hui-Xiong | Yu, Song-Yuan

Article Type: Research Article

Abstract: Endometriosis is one of the most common diseases that happen in reproductive women. The main symptoms include ovarian endometrial cyst, pelvic pain, and so on. We report a case of a 23-year-old woman with a refractory long-course ovarian endometrial cyst (OEC). The patient was previously identified to have a hypoechoic mass sized 9.7 cm in diameter on ultrasound (US) in the right ovary and was tentatively diagnosed as OEC in another tertiary hospital, who was then subjected to US-guided cyst sclerotherapy while the procedure was failed since only a very small amount of viscous and sticky fluid can be aspirated. The …patient was then referred to our hospital for further treatment. Pretreat contrast-enhanced ultrasound (CEUS) showed non-enhancement of the mass with a thin cyst wall and a cyst-in-cyst pattern was observed. The possibility of ovarian malignancy was ruled out and the initial diagnosis of OEC was confirmed. The patient was then subjected to US-guided cyst sclerotherapy with lauromacrogol. The interventional procedure was eventful that no fluid was aspirated as what happened in the previous hospital. Thus urokinase was used to dissolve the old, viscious and sticky blood and finally, all the fluid was aspirated. The total consumption of urokinase was 60,000 U. Then lauromacrogol as a sclerosant was injected into the cyst cavity and the cyst wall was flushed repeatedly with lauromacrogol until the aspirated fluid became light red. Finally, 20 mL lauromacrogol was reserved in the cyst and the interventional procedure cost 2 hours The post-procedure course was uneventful without any discomfort, and the volume reduction rate of the cyst was 54%at 3-month follow-up. The visual analogue scale for the pain decreased from 4 before treatment to 1 after treatment, indicating a successful and effective outcome for the refractory long-course OEC. Show more

Keywords: Contrast-enhanced ultrasound, ovarian endometrial cyst, lauromacrogol, sclerotherapy

DOI: 10.3233/CH-211134

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

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, Iakovos | 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: 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: 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: Wenny, Raphael | Schmidt, Manfred | Zaussinger, Maximilian | Zucal, Isabel | Duscher, Dominik | Huemer, Georg M.

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: 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: Zhang, Wei-Bing | Xu, Wen | Fu, Wen-Jie | He, Bei-Li | Liu, Hua | 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: 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: 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: 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: Luo, Zhi-Yan | Hong, Yu-Rong | Yan, Cao-Xin | Wang, Yong | Ye, Qin | Huang, Pintong

Article Type: Research Article

Abstract: OBJECTIVES: The aim of this study was to find the optimal parameters and cutoffs to differentiate metastatic lymph nodes (LNs) from benign LNs in the patients with papillary thyroid carcinoma (PTC) on the quantitative contrast-enhanced ultrasound (CEUS) features. METHODS: A total of 134 LNs in 105 patients with PTCs were retrospectively enrolled. All LNs were evaluated by conventional ultrasound (US) and CEUS before biopsy or surgery. The diagnostic efficacy of CEUS parameters was analyzed. RESULTS: Univariate analysis indicated that metastatic LNs more often manifested centripetal or asynchronous perfusion, hyper-enhancement, heterogeneous enhancement, ring-enhancing margins, higher PI, …larger AUC, longer TTP and DT/2 than benign LNs at pre-operative CEUS (p  <  0.001, for all). Multivariate analysis showed that centripetal or asynchronous perfusion (OR = 3.163; 95% CI, 1.721–5.812), hyper-enhancement(OR = 0.371; 95% CI, 0.150–0.917), DT/2 (OR = 7.408; 95% confidence interval CI, 1.496–36.673), and AUC (OR = 8.340; 95% CI, 2.677–25.984) were predictive for the presence of metastatic LNs. The sensitivity and accuracy of the quantitative CEUS were higher than qualitative CEUS (75% vs 55 % and 83.6% vs 76.1 % , respectively). CONCLUSIONS: Quantitative CEUS parameters can provide more information to distinguish metastatic from benign LNs in PTC patients; In particular, DT/2 and AUC have a higher sensitivity and accuracy in predicting the presence of metastatic LNs and reduce unnecessary sampling of benign LNs. Show more

Keywords: Contrast-enhanced ultrasound, lymph node metastasis, papillary thyroid carcinoma, ultrasound

DOI: 10.3233/CH-200909

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Zhao, Meng | Zhu, Yunkai | Zhang, Yanhua | Yang, Xupeng | Duan, Yourong | Chen, Yaqing | Sun, Ying

Article Type: Research Article

Abstract: BACKGROUND: Molecular targeted contrast-enhanced ultrasound (CEUS) imaging is a potential imaging strategy to improve the diagnostic accuracy of conventional ultrasound (US) imaging. US contrast agents are usually micrometer-sized and non-target gas bubbles while nano-sized and targeted agents containing phase-shift materials absorb more attractions for their size and the liquid core and excellent molecular imaging effect. METHODS: PLGA12k -mPEG2k -NH2 , DSPE-mPEG2k and perfluorohexan (PFH) were used to construct a new targeted ultrasound contrast agent with CUB domain-containing protein 1 (CDCP1) receptor for the detection and diagnosis of prostate cancer. The potential of tumor-targeted nanoparticles (CDCP1-targeted perfluorohexan-loaded phase-transitional …nanoparticles, anti-CDCP1 NPs) as contrast agents for ultrasound (US) imaging was assessed in vitro . Moreover, studies on the cytotoxicity and the targeting ability of anti-CDCP1 NPs assisted by US were carried out. RESULTS: The results showed that anti-CDCP1 NPs had low cytotoxicity, and with the increasing of polymer concentration in anti-CDCP1 NPs, the CEUS imaging of agent gradually enhanced, and enhanced imaging associated with the length of observing time. Furthermore, it was testified that anti-CDCP1 assisted the agent to target cells expressing CDCP1, which demonstrated the active targeting of anti-CDCP1 NPs in vitro . CONCLUSION: All in all, the feasibility of using targeted anti-CDCP1 NPs to enhance ultrasound imaging has been demonstrated in vitro , which laid a solid foundation for molecular US imaging in vivo , and anti-CDCP1 NPs might have a great clinical application prospect. Show more

Keywords: Targeted nanoparticle, contrast agent, prostate cancer

DOI: 10.3233/CH-200900

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Park, Seong Jun | Yoon, Jung | Seo, Hong Seog | Lim, Chae Seung

Article Type: Research Article

Abstract: BACKGROUND: Platelet function analysis is crucial in assessing the hemostatic status to evaluate congenital and acquired platelet function defects. The Anysis-200 analyzer is a new automated lab-on-a-chip-based platelet function analyzer. OBJECTIVE: We aimed to evaluate a new platelet function analyzing system, the Anysis-200 in comparison to the Platelet Function Analyzer (PFA)-200 in cardiac patients. METHODS: Citrated blood was collected from 174 patients who visited the Department of Cardiology. The Anysis-200 consists of two kits, the microchips with collagen and epinephrine-coated membrane (C/EPI) or adenosine diphosphate-coated membrane (C/ADP). Platelet clogging in the Anysis-200 is measured by the …blood migration distance obtained by a camera, which is compatible with the closure time in the PFA-200. We performed Anysis-200 and PFA-200 analyzers simultaneously and compared the results. RESULTS: The sensitivity and specificity of the Anysis-200 C/EPI kit in comparison to the PFA-200 C/EPI kit were 63.41% and 91.43%, respectively. Regarding the C/ADP kit, the sensitivity and specificity of the Anysis-200 were 58.97% and 74.29%, respectively. The agreement rate between the Anysis-200 and PFA-200 for C/EPI was 83.35% and 70.14% for C/ADP. CONCLUSIONS: The Anysis-200, which applies a novel method to detect platelet clogging, has shown moderate to fair agreement with the PFA-200. This test is potentially useful for screening cardiac patients with an abnormal platelet function. Show more

Keywords: Platelet function, Anysis-200 analyzer, PFA-200 analyzer

DOI: 10.3233/CH-190801

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

Authors: Carlisi, Melania | Mancuso, Salvatrice | Caimi, Gregorio | Siragusa, Sergio

Article Type: Research Article

Abstract: The complement system is an essential component of the innate immune defence that, if overly activated, may damage organs and tissues. For this reason, there is a fine complement regulatory system. The complement modulation system includes two proteins with important regulatory activity, CD55 or decay accelerating factor (DAF) and CD59 or membrane inhibitor of reactive lysis (MIRL). The paroxysmal nocturnal hemoglobinuria (PNH) is a clonal and non-neoplastic disease characterized by intravascular haemolysis, occurrence of thrombosis and bone marrow failure. In clinical practice, in opposition to PNH, a variety of pathological conditions have been observed with an acquired and …non-genetic deficiency of the regulatory proteins CD55 and CD59. This abnormal, non-clonal, reduced expression of complement regulatory proteins configures what we may define as PNH-like phenotype. Similarly to PNH, even in the PNH-like phenotype diseases there has been a greater exposure to the mediated complement cellular lysis and, a likely increased risk of thromboembolic events. Therefore, the knowledge of the potential roles of the complement system becomes necessary for a deeper understanding of several pathological conditions and for an improved clinical management of the patients. Show more

Keywords: Paroxysmal nocturnal hemoglobinuria, complement system, CD55, CD59, thromboembolic risk

DOI: 10.3233/CH-190735

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

Authors: Zhang, Guang | Zhang, Tao | Sun, Xiubin | Tang, Fang | Lin, Haiyan | Liu, Yanxun | Zhang, Chengqi | Xue, Fuzhong

Article Type: Research Article

Abstract: The association between whole blood viscosity (WBV) and metabolic syndrome (MetS) is still scarcely investigated in the population-based prospective cohort. We aim to explore the longitudinal effect of WBV on MetS, and to verify whether WBV measures can be used as early predictors for MetS. The longitudinal cohort consisted of 3,508 adults (2,350 males and 1,158 females) who visited the health check-up system twice. WBV were measured at four shear rate (200, 50, 10 and 1 s-1 ), and their values were classified into quartiles. Multivariate Cox models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence …intervals (CIs) in men and women, respectively. A total of 444 (12.66%) incident MetS were observed at follow-up period. The incidences of MetS significantly increased with increasing quartiles of WBVs at all of the shear rate in men. After adjusting for baseline age, smoking, obesity, hypertension, hyperglycemia, and hyperlipidemia status, all of the WBV measures were significantly associated with incident MetS in men, and the HRs showed clear increasing trend across the quartiles of baseline WBVs. There were no significant association between WBVs and incident MetS in women. These findings suggest that MetS has a hemodynamic basis, and WBVs could be used as independent early predictor for MetS in men. Show more

Keywords: Whole blood viscosity, metabolic syndrome, prospective cohort

DOI: 10.3233/CH-15120

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-170347

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