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

Authors: Jung, Ernst Michael | Moran, Valentina Ocaña | Engel, Martin | Krüger-Genge, Anne | Stroszczynski, Christian | Jung, Friedrich

Article Type: Research Article

Abstract: AIM: To examine to what extent the high frame rate contrast-enhanced ultrasound (HiFR) diagnostic enables the conclusive diagnosis of liver changes with suspected malignancy. MATERIAL/METHODS: Ultrasound examinations were performed by an experienced examiner using a multifrequency probe (SC6-1) on a high-end ultrasound system (Resona 7, Mindray) to clarify liver changes that were unclear on the B-scan. A bolus of 1–2.4 ml of the Sulphur hexafluoride ultrasound microbubbles contrast agent SonoVue™ (Bracco SpA, Italy) was administered with DICOM storage of CEUS examinations from the early arterial phase (5–15 s) to the late phase (5–6 min). Based on the image files stored …in the PACS, an independent reading was performed regarding image quality and finding-related diagnostic significance (0 not informative/non-diagnostic to 5 excellent image quality/confident diagnosis possible). References were clinical follow-up, if possible, comparison to promptly performed computed tomography or magnetic resonance imaging, in some cases also to histopathology. RESULTS: We examined 100 patients (42 women, 58 men, from 18 years to 90 years, mean 63±13 years) with different entities of focal and diffuse liver parenchymal changes, which could be detected in all cases with sufficient image quality with CEUS and with high image quality with HiFR-CEUS. Proportionally septate cysts were found in n  = 19 cases, scars after hemihepatectomy with local reduced fat in n  = 5 cases, scars after microwave ablation in n  = 19 cases, hemangiomas in n  = 9 cases, focal nodular hyperplasia in n  = 8 cases, colorectal metastases in n  = 15 cases, hepatocellular carcinoma (HCC) in n  = 11 cases, Osler disease in n  = 8 cases. The size of lesions ranged from 5 mm to 200 mm with a mean value of 33.1±27.8 mm. Conclusive diagnoses could be made by the experienced investigator in 97/100 cases with CEUS, confirmed by reference imaging, in parts by histopathology or follow-up. The image quality for HiFR CEUS was rated with a score of 3 to 5; 62 cases were assessed with an average of good (4 points), 27 cases with very good (5 points), and in 11 cases (3 points) still satisfactory despite aggravated acoustic conditions. The specificity of HIFR-CEUS was 97%, the sensitivity 97%, the positive predictive value 94%, the negative predictive value 99% and the accuracy 97% . CONCLUSION: HIFR-CEUS has demonstrated has demonstrated an improved image quality resulting in a high diagnostic accuracy. In the hands of an experienced investigator, HiFR-CEUS allows the assessment of focal and diffuse unclear liver parenchymal changes on B-scan and dynamic assessment of microcirculation in solid and vascular changes. Show more

Keywords: Contrast-enhanced ultrasound sonography –CEUS –high frame rate contrast-enhanced (HiFR) –liver cancer

DOI: 10.3233/CH-221449

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2022

Authors: Liu, Fang | Gao, Bo | Wang, Yu

Article Type: Research Article

Abstract: BACKGROUND: Atherosclerosis (AS) is a common inflammatory cardiovascular disease, and circular RNAs (circRNAs) are associated with the pathogenesis of AS. CircRNA Interleukin (IL)-1 receptor-associated kinase 1 (circIRAK1, hsa_circ_0091822) was upregulated in AS. The aims of this study were to ascertain the function and mechanism of circIRAK1 in AS. METHODS: Human Umbilical Vein Endothelial Cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL). RNA expression was detected by reverse transcription-quantitative polymerase chain reaction assay. Cell viability was examined using Cell Counting Kit-8 assay. Tube formation ability was measured by tube formation assay. Cell apoptosis was assessed using flow cytometry. …Western blot was used for protein detection. Inflammatory reaction was evaluated via Enzyme-linked immunosorbent assay. Oxidative injury was analyzed by commercial kits. Target binding was determined through dual-luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay. RESULTS: The expression of circIRAK1 was upregulated in AS serums and ox-LDL-treated HUVECs. Silencing circIRAK1 enhanced cell viability and angiogenesis while suppressed cell apoptosis, inflammatory response and oxidative stress in ox-LDL-stimulated HUVECs. CircIRAK1 served as a molecular sponge for miR-330-5p. CircIRAK1 regulated ox-LDL-mediated cell injury by absorbing miR-330-5p. In addition, miR-330-5p prevented endothelial cell dysfunction caused by ox-LDL via targeting tripartite motif containing 14 (TRIM14). TRIM14 expression was upregulated by circIRAK1 through sponging miR-330-5p. CONCLUSION: These results suggested that circIRAK1 upregulated TRIM14 by interacting with miR-330-5p, consequently contributing to ox-LDL-induced endothelial cell injury in AS. Show more

Keywords: circIRAK1, atherosclerosis, miR-330-5p, TRIM14

DOI: 10.3233/CH-221551

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2022

Authors: Zheng, Ruiying | Ye, Jieyi | Zhang, Xiaoer | Zhou, Xiaoyu | Huang, Tongyi | Xu, Ming | Cong, Longfei | Xie, Xiaoyan | Huang, Guangliang

Article Type: Research Article

Abstract: BACKGROUND: Registration of three-dimensional contrast-enhanced ultrasound fusion imaging (3DCEUS-FI) is time-consuming to obtain high success rate. OBJECTIVE: To investigate the influence factors on registration success rate of 3DCEUS-FI. METHODS: Water tank phantoms were made to obtain mimicked pre- and post- radiofrequency ablation three-dimensional contrast-enhanced ultrasound (3DCEUS) and CT images. Orthogonal trials were designed according to factors including size, depth, enhancement level of mimicked tumor, diameter and number of mimicked adjacent vessels. Mimicked pre- and post-RFA 3DCEUS images of 72 trials were fused to assess ablative margin (AM) by two radiologists. With CT images as standard, 3DCEUS-FI …accuracy was considered as the consistency of AM evaluation. The inter-observer agreement and the influence factors on registration success rates were analyzed. RESULTS: The intraclass correlation coefficient (ICC) for the consistency of AM evaluation between CT and 3DCEUS-FI in x-axis, y-axis or z-axis was 0.840∼0.948 (P  <  0.001). The ICC for inter-observer agreement was 0.840∼0.948 (P  <  0.001). The success rates of registration within mimicked vessels with diameter of 2 mm were significantly lower than those with diameter of 3 mm and 4 mm. CONCLUSIONS: The mimicked AM measured by 3DCEUS-FI had high accuracy and inter-observer agreement. Diameter of the mimicked adjacent vessels was significantly related to success rate of registration. Show more

Keywords: Contrast-enhanced ultrasound, three-dimensional, fusion imaging, phantom, registration

DOI: 10.3233/CH-221573

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Zhong, Lichang | Xie, Juan | Shi, Lin | Gu, Liping | Bai, Wenkun

Article Type: Research Article

Abstract: OBJECTIVE: To establish a nomogram for predicting cervical lymph node metastasis (CLNM) based on the preoperative conventional ultrasound (US) and shear wave velocity (SWV) features of papillary thyroid carcinoma (PTC). METHODS: A total of 101 patients with pathologically confirmed thyroid nodules were enrolled. These patients were divided into the CLNM-positive (n  = 40) and CLNM-negative groups (n  = 61). All patients underwent the preoperative conventional US and shear wave elastography (SWE) evaluation, and the US parameters and SWV data were collected. The association between SWV ratio and CLNM was compared to assess the diagnostic efficacy of SWV ratio alone as …opposed to SWV ratio in combination with the conventional US for predicting CLNM. RESULTS: There were significant differences in shape, microcalcification, capsule contact, SWV mean, and SWV ratio between the CLNM-positive and CLNM-negative groups (P  <  0.05). Logistic regression analysis showed that taller-than-wide shape, microcalcification, capsule contact, and SWV ratio >  1.3 were risk factors for CLNM; Logistic(P)=-6.93 + 1.647 * (microcalcification)+1.138 * (taller-than-wide-shape)+1.612 * (capsule contact)+2.933 * (SWV ratio >  1.3). The area under the curve (AUC) of the receiver operating characteristic (ROC) of the model for CLNM prediction was 0.87, with 81.19% accuracy, 77.5% sensitivity, and 85.25% specificity. CONCLUSION: The nomogram based on conventional US imaging in combination with SWV ratio has the potential for preoperative CLNM risk assessment. This nomogram serves as a useful clinical tool for active surveillance and treatment decisions. Show more

Keywords: Nomogram, papillary thyroid carcinoma, central lymph node metastasis, shear wave velocity, conventional ultrasound

DOI: 10.3233/CH-221576

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2022

Authors: Wei, Wenbo | Tang, Min | Wang, Qi | Li, Xiaoming

Article Type: Research Article

Abstract: BACKGROUND: Coronary artery disease (CAD) is a common coronary artery disease. The functional mechanism of circular RNA (circRNA) HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 (circ_HECW2, hsa_circ_0057583) in ox-LDL-treated human cardiac microvascular endothelial cells (hCMECs) is still unclear. METHODS: Expression levels of circ_HECW2, microRNA (miR)-942-5p, and toll-like receptor 4 (TLR4) were analyzed by quantitative real-time PCR (qRT-PCR) and western blot assays. Cell proliferation and apoptosis were analyzed by 5-ethynyl-2’-deoxyuridine (EdU) assay, cell counting kit-8 (CCK8) assay, and flow cytometry, respectively. Tube formation assay was performed to analyze the angiogenesis of cells. Luciferase reporter and …RNA pull-down assays were performed to analyze the target relationship among circ_HECW2, miR-942-5p and TLR4. RESULTS: Circ_HECW2 and TLR4 expression levels were up-regulated and miR-942-5p expression was decreased in the serum of CAD patients and oxidized low-density lipoprotein (ox-LDL)-induced hCMECs. Knockdown of circ_HECW2 enhanced cell proliferation and inhibited cell apoptosis in ox-LDL-treated hCMECs. MiR-942-5p was the target of circ_HECW2 and directly targeted TLR4. Moreover, the effect of circ_HECW2 knockdown could be weakened by anti-miR-942-5p, and TLR4 could restore the function of miR-942-5p on cell damage of ox-LDL-induced hCMECs. CONCLUSION: Circ_HECW2 could regulate ox-LDL-induced cardiovascular endothelial cell dysfunction through targeting miR-942-5p/TLR4 axis. Show more

Keywords: Circ_HECW2, miR-942-5p, TLR4, coronary artery disease

DOI: 10.3233/CH-221550

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2022

Authors: Chkhitauri, Lela | Sanikidze, Tamar | Giorgadze, Elene | Asatiani, Ketevan | Kipiani, Nana | Momtselidze, Nana | Mantskava, Maka

Article Type: Research Article

Abstract: BACKGROUND: Prevention of Type 2 diabetes mellitus (T2DM) requires a modifying effect on the pathological processes inducing the β-cell dysfunction. OBJECTIVES: the comprehensive study of the violation of rheological parameters in patients with different stages of diabetes and identification of possible links between these alterations with the intensity of the oxidative stress in the patient’s body. METHODS: 60 patients with IR, prediabetes, T2DM and healthy volunteers were included. Full range of the rheological parameters of the patients’ blood - the indicators of erythrocytes aggregation index (EAI), the relative deformability of the erythrocytes membranes (ERDI), blood plasma …viscosity (BPV), and oxidative stress intensity (OSI) were examined. RESULTS: In patients with insulin resistance (IR), prediabetes, and T2DM the ERDI was statistically significantly lower and BPV - higher compared to control; a significant increase in EAI was detected in the patient group with prediabetes and T2DM compared to the control. CONCLUSION: The level of rheological disorders in patients increases with the increase of the level of carbohydrate metabolism disorders and intensity of oxidative stress and reaches a maximum during manifested diabetes. Diagnosis of hemorheological disorders and OSI in T2DM can serve as an early marker of target organ damage possibility. Show more

Keywords: Insulin resistance, prediabetes, Type 2 diabetes mellitus (T2DM), rheological parameters, oxidative stress

DOI: 10.3233/CH-221512

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Li, Qi | Nie, Fang | Yang, Dan | Dong, Tiantian | Liu, Ting

Article Type: Research Article

Abstract: OBJECTIVES: To explore the feasibility of contrast-enhanced ultrasound (CEUS) as a new tool for characterizing vascularization of primary peripheral lung cancer. METHODS: 315 consecutive patients with definite primary peripheral lung cancers underwent CEUS examination from November 2016 to March 2022. CEUS parameters including time to enhancement (TE), time to peak (TP), time to wash-out (TW), distribution of vessels (DV), extent of enhancement (EE) and homogeneity of enhancement (HE) were obtained. RESULTS: The lesions were grouped on the basis of TE which reflects tumor vascularization: early enhancement (pulmonary arterial vascularization) (n  = 91) and delayed enhancement group (bronchial …arterial vascularization) (n  = 224). Overall, lung tumors commonly (71.1%) manifested a delayed enhancement which indicating blood supply originated from bronchial arteries, while an early enhancement was present in less than a third of the cases. Tumors with bronchial vascularization tended to show a delayed, reduced and heterogeneous enhancement. Correspondingly, it is characterized by a shorter TE, marked EE and a relatively infrequent occurrence of necrosis in tumors with pulmonary vascularization. CONCLUSIONS: Providing micro-perfusion information, CEUS is a potentially imaging tool for evaluating blood supply in primary peripheral lung cancer. Show more

Keywords: Contrast-enhanced ultrasound, tumor vascularization, lung cancers

DOI: 10.3233/CH-221484

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Chen, Jie | Zhang, Bo

Article Type: Research Article

Abstract: Hereditary hemorrhagic telangiectasis (HHT) is an autosomal dominant hereditary disease, which can lead to abnormal angiogenesis. We performed contrast-enhanced ultrasound (CEUS) in a patient with HHT represented with hemothorax. After targeted embolization, the condition of hemothorax improved. In this case, we explore the use of CEUS to locate the responsible vessel of hemothorax, and found that CEUS could be used as a complementary preoperative method of localization with Computed tomography angiography (CTA).

Keywords: Contrast-enhanced ultrasound, hereditary hemorrhagic telangiectasis, hemothorax

DOI: 10.3233/CH-221646

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2022

Authors: Chen, Wanjiao | Hu, Bin | Zhang, Shuya | Zheng, Ying | Zhou, Zhong | Mai, Yifeng

Article Type: Research Article

Abstract: BACKGROUND: Accumulating evidence shows that the increase in blood viscosity (BV) is an independent risk factor for atherosclerosis and its related diseases, but as far as we know, there are few studies on the relationship between blood viscosity and carotid plaque severity. Therefore, we aimed to investigate the relationship between blood viscosity and the presence of carotid plaques, and further explore its relationship with the severity of carotid plaques. METHODS: We retrospectively analyzed the data of consecutive subjects in the physical examination center of the Affiliated Hospital of Ningbo University Medical College from January 2022 to May 2022. …The parameters of blood viscosity include the whole blood viscosity (WBV) at high, middle, and low shear rate, plasma viscosity (PV), hematocrit (HCT), rigidity “k”, rigidity index (RI), aggregation index (AI) and electrophoresis rate (ER), and standardized BV calculated by Quemada’s equation were included in the study. Carotid plaque score (CPS) was used to measure the severity of carotid artery disease, and participants were divided into mild, moderate, and severe groups according to the quartile of the score. Independent samples t -test and one-way ANOVA were used to compare normally distributed continuous variables between two or more independent groups, respectively. Binary logistic regression was used to evaluate the risk factors of carotid plaque. RESULTS: 314 men were enrolled in the study, of which 165 participants were diagnosed with Carotid artery plaque (CAP) (66.9%). Compared with the CAP- group, the WBV and PV of the CAP+group decreased, but the difference only existed in the PV (p  = 0.001). However, standardized BV values (HCT set at 0.45) were higher in the CAP+group than in the CAP- group (3.8643±0.35431vs 3.9542±0.64871, p  = 0.188). Regarding the rigidity and aggregation of RBC, the parameters including rigidity “k”, RI, AI and ER increased in the CAP+group compared with the CAP- group. The difference was statistically significant in k and ER (p  = 0.04, p  = 0.009). To assess the severity of carotid plaque, we divided the participants into mild, moderate, and severe groups by using the tertile of CPS value. The mild group was defined as CPS≤0.5 (n  = 108), the moderate group as 0.5 <  CPS≤1.7 (n  = 105), and the severe group as CPS >  1.7 (n  = 101). It was found that WBV and PV decreased with the increase of plaque severity, but the difference among the three groups was significant in PV (F  = 8.073, p  <  0.0001). In addition, with the severity of plaque from mild to severe, standardized BV gradually increased, which were 3.8611±0.34845, 3.8757±0.36637, 3.9007±0.38353 respectively. The difference between the groups was close to statistically significant (F  = 2.438, p  = 0.089). The values of parameters describing erythrocyte aggregation and rigidity increased among the mild, moderate, and severe groups. The difference was statistically significant in RBC rigidity “k” and ER of RBC (F  = 3.863, p  = 0.022; F  = 5.897, p  = 0.003, respectively). CONCLUSION: Increased blood viscosity is a risk factor for carotid plaque, but its increase may be hidden by decreased hematocrit. Therefore, it is necessary to comprehensively analyze various parameters of blood viscosity, such as the standardized BV calculated by Quemada’s equation, which may provide more useful reference value. Show more

Keywords: Carotid plaque, blood viscosity, hematocrit, Quemada’s equation

DOI: 10.3233/CH-221597

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2022

Authors: Shafie, Neda | Kordi, Negin | Gadruni, Keivan | SalehFard, Ziba | Jung, Friedrich | Heidari, Naser

Article Type: Research Article

Abstract: BACKGROUND: Physical training in patients with heart failure can affect hemodynamic, cardiac and angiogenesis parameters. OBJECTIVE: The aim of the present study was to investigate the effects of traditional moderate-intensity rehabilitation training and interval training on some angiogenesis factors in coronary artery bypass graft (CABG) patients. METHODS: Thirty CABG patients (mean age±SD, 55±3 years) were randomly assigned to one of three groups: high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) or the control group. After the initial assessments, eligible patients in the experimental groups (HIIT and MICT) performed exercise training for 8 weeks, while the …control group did not. Angiogenesis and angiostatic indices, including pro-adrenomedullin (pro-ADM), basic fibroblast growth factor (bFGF), and endostatin, were then measured. RESULTS: The results showed no significant difference between pro-ADM in the HIIT and MICT groups (P  = 0.99), but a significant difference was found between MICT and the control group and between HIIT and the control group (P  = 0.001). There is also no significant difference between the bFGF levels in the HIIT and MICT training groups (P  = 1.00), but the changes in this factor between the training groups and the control group were significant (P  = 0.001). There was a significant difference between the levels of endostatin in all three groups. CONCLUSIONS: Two methods of cardiac rehabilitation (HIIT and MICT) may be useful for the recovery of patients with coronary artery bypass grafting. This improvement manifested itself in changes in angiogenesis and angiostatic indices in this study. However, more extensive studies are needed to investigate the effects of these two types of rehabilitation programs on other indicators of angiogenesis and angiostatic. Show more

Keywords: Training, angiogenesis, cardiovascular, endostatin, pro-adrenomedullin

DOI: 10.3233/CH-221605

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Toprak, Kenan | Kaplangoray, Mustafa | Palice, Ali | İnanır, Mehmet | Memioğlu, Tolga | Kök, Zafer | Altıparmak, İbrahim Halil | Toprak, İbrahim Halil | Biçer, Asuman | Demirbağ, Recep

Article Type: Research Article

Abstract: BACKGROUND: Complete atrioventricular block is most commonly caused by age-related degeneration and fibrosis in the cardiac conduction system and is called primary idiopathic complete atrioventricular (iCAVB). Although many factors affect this situation, which increases with age in the cardiac conduction system, the relationship between whole blood viscosity (WBV) and iCAVB has not been clarified until now. In this study, we aim to reveal the relationship between iCAVB and WBV. METHODS AND RESULTS: 141 patients with dual-chamber permanent pacemaker implanted for iCAVB and 140 age- and sex-matched subjects were included in this study. The WBV values of the study …groups were compared in both high shear rate (HSR) and low shear rate (LSR). Both WBV at HSR and WBV at LSR were significantly higher in the iCAVB group compared to the control group (16.11 [15.14–16.89] vs 14.40 [13.62–15.58]; 39.82 [17.43–55.23] vs 1.38 [–13.14–26.73]; p  <  0.001, respectively). The patient population was followed up for an median of 38 months for all-cause mortality. Higher mortality rates were found in higher WBV at HSR and WBV at LSR (p  <  0.001,for both). CONCLUSIONS: In this study, WBV was found to be an independent predictor for iCAVB, and in these patients WBV was associated with poor clinical outcomes. Show more

Keywords: Primary idiopathic complete atrioventricular block, whole blood viscosity, high shear rate, low shear rate

DOI: 10.3233/CH-221596

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2023

Authors: Qiu, Yi-Jie | Cheng, Juan | Zuo, Dan | Zhang, Qi | Tian, Xiao-Fan | Lu, Xiu-Yun | Chen, Sheng | Dong, Yi | Wang, Wen-Ping

Article Type: Research Article

Abstract: OBJECTIVE: To explore the value of vascular architecture detected by micro vascular imaging (MVI) in preoperative diagnosis of focal liver lesions (FLLs). METHODS: In this retrospective study, patients with surgery and histopathologically proved or radiologically confirmed FLLs were included. Vascular architecture of FLLs were acquired by color Doppler flow imaging (CDFI) and MVI on LOGIQ™ E20 ultrasound machine (C1–6 convex array probes). Alder semiquantitative analysis (grade 0–3) and morphologic features of blood vessels (pattern a–f) were used to assess the blood flow within the FLLs. Interobserver agreement for evaluating blood flow of FLLs was analyzed. Using Adler’s grading …or morphologic patterns as diagnostic criteria for malignant FLLs, the diagnostic efficiency was analyzed and compared. RESULTS: From October 2021 and February 2022, 50 patients diagnosed with 40 malignant FLLs and 10 benign FLLs were finally included. The Kappa value within two observers for evaluating the blood flow of FLLs was 0.78 for MVI and 0.55 for CDFI. According to Alder semiquantitative analysis, more high-level blood flow signals (grade 2–3) were detected by MVI than CDFI (P  <  0.05). Based on high-level blood flow signals (grade 2–3) and hypervascular supply patterns (pattern e and f), the diagnostic accuracy for malignant FLLs were 76% and 68% for MVI, 56% and 38% for CDFI, respectively. CONCLUSION: MVI is superior to CDFI in evaluating vascular architecture of FLLs. The high-level flow signals and hypervascular pattern detected by MVI have a useful and complementary value in preoperative non-invasive identification of malignant FLLs. Show more

Keywords: Micro vascular imaging (MVI), color Doppler flow imaging (CDFI), focal liver lesions (FLLs), blood flow, vascular architectures

DOI: 10.3233/CH-221682

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Huang, Yunlin | Wang, Ying | Liu, Lingxiao | Zhu, Lei | Qiu, Yijie | Zuo, Dan | Lu, Xiuyun | Dong, Yi | Jung, Ernst-Michael | Wang, Wenping

Article Type: Research Article

Abstract: OBJECTIVES: To explore the potential added value of dynamic contrast enhanced ultrasound (DCE-US) using VueBox® software for the diagnosis of small solid thyroid nodules (≤1.0 cm). PATIENTS AND METHODS: This prospective study was approved by the institutional review board and it was performed at two hospitals from January 2020 to October 2020. B mode ultrasound and contrast enhanced ultrasound (CEUS) images were obtained for 79 small solid thyroid nodules (≤1.0 cm) confirmed by ultrasound-guided fine needle aspiration cytology results in 79 consecutive patients (55 women and 24 men, median age: 41 years). The CEUS time-intensity curves (TICs) of thyroid nodules …and surrounding parenchyma were created by VueBox® software (Bracco, Italy). The CEUS quantitative parameters were obtained after curve fitting. The diagnostic efficiency of the diagnostic performance of CEUS and DCE-US was evaluated and compared. The weighted kappa statistic (κ) was performed to assess the interobserver agreement and consistency between the diagnosis of CEUS and DCE-US. RESULTS: Among the 79 thyroid nodules, 56 (70.9 %) were malignant and 23 (29.1 %) were benign lesions. Hypoenhancement during the arterial phase of CEUS was associated with malignancy (P  <  0.001), with an AUC of 0.705 (sensitivity 71.4 %, specificity 69.6 %). Among all CEUS quantitative parameters, the peak enhancement (PE), wash-in rate (WiR), and wash-out rate (WoR) of DCE-US in malignancies were significantly lower than those in benign nodules (P  = 0.049, P  = 0.046, and P  = 0.020, respectively). The AUCs of PE, WiR, and WoR were 0.642 (sensitivity 65.2 %, specificity 67.9 %), 0.643 (sensitivity 43.5 %, specificity 91.1 %), and 0.667 (sensitivity 69.6 %, specificity 69.6 %) in differentiation between benign and malignant small solid thyroid nodules (≤1.0 cm), respectively. Comparing the quantitative parameters of DCE-US between small solid thyroid nodules and surrounding normal thyroid parenchyma, the PE, WiAUC, WiR, WiPI, WoAUC, WiWoAUC, and WoR of the nodules were significantly lower than those of normal thyroid tissue (P  = 0.008, P  <  0.001, P  = 0.037, P  = 0.009, P  = 0.003, P  = 0.002, P  = 0.049, respectively). A total of 16 (20.3 %) nodules showed isoenhancement during the arterial phase of CEUS, while the median PE ratio of surrounding tissue and thyroid nodules was 1.70 (IQR: 1.33–1.89). CONCLUSIONS: VueBox® is a helpful tool for the evaluation of dynamic microvascularization of thyroid nodules, and DCE-US using VueBox® perfusion analysis could provide added values for differential diagnosis of small solid thyroid nodules (≤1.0 cm). Show more

DOI: 10.3233/CH-221681

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Schleder, Stephan | Jung, Ernst-Michael | Schicho, Andreas | Schreyer, Andreas G. | Habicher, Werner | Grassinger, Jochen | Dollinger, Marco

Article Type: Research Article

Abstract: BACKGROUND: Cervical lymphadenopathy can be benign or malignant. Its accurate diagnosis is necessary to determine appropriate treatment. Ultrasound-guided core needle biopsies (US-CNBs) are frequently used as a percutaneous sampling approach. OBJECTIVES: Our aim was to identify the efficacy and safety of US-CNBs in 125 patients with cervical lymphadenopathy and clinically suspected head and neck cancer during the COVID-19 pandemic with limited surgical resources. METHODS: US-CNBs of pathological lymph nodes were performed in 146 lymph nodes on 125 patients. Biopsies were performed ultrasound-guided with a reusable gun core biopsy system and a 10-cm-long 16-G needle. Standard of …reference for the histological findings were panendoscopy, clinical and sonographic follow-up, surgical biopsy or a repeat US-CNB. RESULTS: Adequate material for histologic diagnosis was obtained in 111 patients (89%), of these 83 patients (75%) were diagnosed as malignant, whereas benign lymphadenopathy accounted for 28 patients (25%). Therefore, US-CNB was able to identify malignant or benign lymphadenopathy with an overall accuracy of 88% and 90%, respectively. CONCLUSIONS: Percutaneous US-CNB is a safe and effective alternative to surgical biopsy in the management of cervical lymphadenopathy in patients with clinically suspected head and neck cancer in a setting with limited resources. Show more

DOI: 10.3233/CH-221680

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: He, Dequan | Li, Zhiliang | Chen, Youquan | Huang, Ming

Article Type: Research Article

Abstract: BACKGROUND: Dysfunction of endothelial cells is now considered a vital contributor to the pathogenesis of atherosclerosis (AS). Moreover, circular RNA (circRNA) circ_0029589 has been found to be involved in the regulation of oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell damage. Nevertheless, its molecular mechanism in ox-LDL-triggered endothelial cell injury is poorly defined. METHODS: Human umbilical vein endothelial cells (HUVECs) treated with ox-LDL were applied as cell models of AS. Circ_0029589, microRNA-1197 (miR-1197), and Ras-related protein Rab-22A (RAB22A) expression were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, angiogenesis, and invasion were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium …bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, tube formation, and transwell assays. Western blot analysis of Cleaved-caspase-3, B-cell lymphoma-2 related X protein (Bax), and RAB22A. IL-6, IL-1β, and Tumor necrosis factor α (TNF-α) levels were gauged using ELISA kits. Superoxide Dismutase (SOD) activity and Malondiahyde (MDA) level were assessed using special kits. Bioinformatics software predicted the binding between miR-1197 and circ_0029589 or RAB22A, which was proved using dual-luciferase reporter and RNA pull-down assays. RESULTS: Circ_0029589 and RAB22A expression were strengthened, and miR-1197 was reduced in ox-LDL-treated HUVECs. Importantly, circ_0029589 silencing ameliorated ox-LDL-triggered HUVEC damage via promoting cell proliferation, tube formation ability, invasion, and repressing cell apoptosis, inflammation, and oxidative stress. Mechanical analysis suggested that circ_0029589 might affect RAB22A content through sponging miR-1197. CONCLUSION: Circ_0090231 might protect against ox-LDL-mediated HUVEC injury via the miR-1197/RAB22A axis, which provides a therapeutic strategy for endothelial cell damage of AS. Show more

Keywords: Circ_0029589, miR-1197, RAB22A, ox-LDL, atherosclerosis

DOI: 10.3233/CH-221657

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2023

Authors: Teng, Yanling | Ren, Fei | Wang, Yanan | Xu, Hua | Song, Hejian

Article Type: Research Article

Abstract: BACKGROUND: Previous data have shown that circ_0033596 is involved in the pathogenesis of atherosclerosis (AS). The study aims to reveal the detailed mechanism of circ_0033596 in AS. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish an AS cell model. Quantitative real-time polymerase chain reaction and western blot were implemented to detect the expression of circ_0033596, miR-637, growth factor receptor bound protein2 (GRB2), BCL2-associated x protein (Bax) and B-cell lymphoma-2 (Bcl-2). Cell viability, proliferation, apoptosis and tube formation were investigated by cell counting kit-8, EdU assay, flow cytometry and tube formation …assay, respectively. The production of interleukin (IL-6) and tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay. Oxidative stress was evaluated by lipid peroxidation malondialdehyde assay kit and superoxide dismutase activity assay kit. Dual-luciferase reporter assay, RNA pull-down assay and RIP assay were performed to identify the associations among circ_0033596, miR-637 and GRB2. RESULTS: The expression of circ_0033596 and GRB2 was significantly increased, while miR-637 was decreased in the blood of AS patients and ox-LDL-induced HUVECs compared with controls. Ox-LDL treatment inhibited HUVEC viability, proliferation and angiogenic ability and induced cell apoptosis, inflammation and oxidative stress, while these effects were attenuated after circ_0033596 knockdown. Circ_0033596 interacted with miR-637 and regulated ox-LDL-induced HUVEC damage by targeting miR-637. In addition, GRB2, a target gene of miR-637, participated in ox-LDL-induced HUVEC injury by combining with miR-637. Importantly, circ_0033596 activated GRB2 by interacting with miR-637. CONCLUSION: Circ_0033596 depletion protected against ox-LDL-induced HUVEC injury by miR-637/GRB2 pathway, providing a therapeutic target for AS. Show more

Keywords: AS, circ_0033596, miR-637, GRB2

DOI: 10.3233/CH-221686

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2023

Authors: Binneboessel, Stephan | Masyuk, Maryna | Piayda, Kerstin | Bruno, Raphael Romano | Wernly, Bernhard | Jirak, Peter | Wolff, Georg | Gerdes, Norbert | Baldia, Philipp Heinrich | Kelm, Malte | Nienhaus, Fabian | Lang, Alexander | Winkels, Holger | Geerling, Gerd | Guthoff, Rainer | Kaya, Sema | Flossmann, Gerald | Riemer, Thomas | Baertschi, Michael | Jung, Christian

Article Type: Research Article

Abstract: BACKGROUND: “Spaceflight associated neuro-ocular syndrome” (SANS) represents a challenging health condition in modern space medicine. Forty-eight percent of astronauts are diagnosed with SANS after long-term space missions. The pathophysiological mechanism seems to be multifactorial, and yet remains unknown. In this proof-of-concept study we plan to investigate retinal microcirculatory changes in weightlessness and aim to identify their role in the development of SANS. METHODS AND DESIGN: Healthy individuals will take part in a parabolic flight campaign, which recreates fractioned total weightlessness periods. The airplane is specifically equipped, and designed for the execution of parabolic flight maneuvers and scientific research …in microgravity. Retinal microcirculation will be assessed with a modified fundus camera, which allows dynamic vessel analysis. We will additionally measure intra-ocular pressure and hemodynamic changes during each phase of the flight. Blood samples will be analyzed at baseline, one hour and 24 hours after exposure to weightlessness. CONCLUSIONS: This pilot study aims to investigate the feasibility of retinal microcirculation assessment during varying gravity. Results of this study may generate insights whether venous stasis in the eye, surrogated by the dilatation of retinal vessels and increase in intraocular pressure as signs of venous insufficiency, may potentially contribute to the development of SANS. Show more

Keywords: Microgravity, parabolic flight campaign, retinal microcirculation, dynamic vessel analyzer, spaceflight associated neuro-ocular syndrome

DOI: 10.3233/CH-221691

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2023

Authors: Hojker, Marta | Tršan, Jure | Tršan, Uroš | Gale, Ana | Jerman, Alexander | Košuta, Daniel

Article Type: Research Article

Abstract: BACKGROUND: The predictive value of coagulation markers for venous thromboembolism (VTE) in Covid-19 patients has been investigated with conflicting results. OBJECTIVE: Our aim was to investigate the correlation between biomarkers and VTE and the predictive value of D-dimer for VTE in hospitalized Covid-19 patients. METHODS: Complete blood count, inflammatory and coagulation biomarkers at admission were collected. VTE was defined as diagnosed pulmonary embolism or deep vein thrombosis. Events were defined as in-hospital death or ICU admission. Predictors of VTE were identified with Pearson prediction models. A ROC curve was constructed to assess the predictive value of …D-dimer. RESULTS: 1651 participants were included, 111 VTE were identified. Events incidence was higher in the VTE group (49.5% vs 28.2%, p  <  0.001). Neutrophil-lymphocyte ratio (NLR, 0.001; 95% CI 0.000–0.002; p 0.019) and D-dimer (0.00005; 95% CI 0.00002–0.00008; p  <  0.001), Geneva score (0.026; 95% CI 0.012–0.040; p  <  0.001) and Wells score (0.047; 95% CI 0.033–0.061; p  <  0.001) were associated with VTE. D-dimer had a goor predictive value for VTE (ROC area 0.85, 95% CI 0.816–0.893), with an optimal cut-off value of 2677μg/L (Youden index of 0,602). CONCLUSIONS: Among coagulation biomarkers D-dimer had the best predictive value for VTE, but higher cut-off values should be used in Covid-19. Show more

Keywords: D-dimer, venous thromboembolism, Covid-19, neutrophil-lymphocyte ratio, inflammatory biomarkers, coagulation biomarkers

DOI: 10.3233/CH-221664

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Caimi, G. | Carlisi, M.

Article Type: Research Article

Abstract: According to Wells classification, it is possible to distinguish the primary hyperviscosity syndromes in polycythemic, sclerocythemic and sieric and/or plasmatic. In polycythemia vera, multiple myeloma, Waldenström’s macroglobulinemia, and monoclonal gammopathy of undetermined significance, we have observed an unexpected behaviour of the erythrocyte deformability. This data highlights that the hemorheological alteration present in polycythemia vera has not been related to the increase of RBC mass only, as well as that present in plasmacellular dyscrasias has not been attributable to the increase of plasma viscosity only. The aim of this paper is to suggest some starting points for an accurate reflection, …emphasizing the need of a revision of the current classification of primary hyperviscosity syndromes. Show more

Keywords: Erythrocyte deformability, primary hyperviscosity syndromes, polycythemia vera, multiple myeloma, Waldenström’s macroglobulinemia, monoclonal gammopathy of undetermined significance

DOI: 10.3233/CH-221549

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2023

Authors: Zhu, Lingfeng | Zhao, Ping | Meng, Xianwei | Jin, Hong | Tuo, Baojuan

Article Type: Research Article

Abstract: BACKGROUND: Endothelial dysfunction is considered to be an important factor in the pathogenesis of atherosclerosis. Circular RNAs (circRNAs) have been confirmed to participate in the development of atherosclerosis. Nevertheless, the role and mechanism of circ_0091822 in atherosclerosis have not been studied yet. METHODS: The expression of circ_0091822, miR-661 and RAB22A were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were estimated by enzyme-linked immunosorbent assay (ELISA). Cell viability was analyzed by Cell Counting Kit-8 (CCK-8) assay, cell proliferation was evaluated by EdU assay, and cell apoptosis was gauged …by flow cytometry. Western blot was performed to assess the protein levels of Bax, Cleaved-caspase-3 and RAB22A. The interaction among miR-661 and circ_0091822 or RAB22A was verified by dual-luciferase reporter assay RESULTS: Ox-LDL enhanced the expression of circ_0091822 in HUVECs. It also constrained proliferation, promotes apoptosis and inflammation in HUVECs, and down-regulation of circ_0091822 attenuated these effects. Mechanically, circ_0091822 could serve as a sponge of miR-661, miR-661 interference rescued circ_0091822 inhibition-mediated effect on the biological functions in ox-LDL-induced HUVECs. Additionally, RAB22A was a target of miR-661, and its overexpression could partially overturn the negative regulation of miR-661 on ox-LDL-treated HUVECs injury. Importantly, circ_0091822 sponged miR-661 to positively regulate RAB22A expression. CONCLUSION: Circ_0091822 contributed to cell injury by targeting miR-661/RAB22A axis in ox-LDL-stimulated HUVECs. Show more

Keywords: AS, circ_0091822, miR-661, RAB22A

DOI: 10.3233/CH-221453

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2022

Authors: Martocchia, Antonio | Piccoli, Cinzia | Notarangelo, Michele Fortunato | Bentivegna, Enrico | Sergi, Daniela | Luciani, Michelangelo | Barlattani, Michela | Sesti, Giorgio | Martelletti, Paolo

Article Type: Research Article

Abstract: BACKGROUND: The use of the ultrasound (US) bedside examination is increasing for the detailed evaluation of the hemodynamic parameters, allowing the physicians to set the appropriate therapeutic strategies with greater precision. OBJECTIVE: The aim of this study is to evaluate the hemodynamic parameters (the cardiac output or CO, the central venous pressure or CVP and the systemic vascular resistance or SVR) in the patients with sepsis, by using a bedside US approach. METHODS: We consecutively enrolled n.82 patients of S.Andrea Hospital (n.47 with sepsis and n.35 without sepsis), examining the hemodynamic parameters by a bedside US …evaluation. RESULTS: The incidence of sepsis was more than 50% of cases. The patients with sepsis presented higher comorbidity and polypharmacy (p  <  0.01, p  <  0.001), with increased creatinine (p  <  0.001) and esteemed glomerular filtration rate (p  <  0.01), C-reactive protein (p  <  0.01), SOFA (Sepsis-related Organ Failure Assessment) score (p  <  1.58×10–7 ) and reduced SVR (p  <  0.05). The SOFA score was inversely related to the SVR (p  <  0.05). CONCLUSIONS: To our best knowledge, this is the first study with a bedside US protocol to measure SVR, beyond the abdominal and cardiac qualitative evaluation. Show more

DOI: 10.3233/CH-221613

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2022

Authors: Kruit, Anne Sophie | Hummelink, Stefan | Eshuis, Lilian | Kusters, Benno | Ulrich, Dietmar

Article Type: Research Article

Abstract: BACKGROUND: Extracorporeal perfusion (ECP) is a promising technique for prolonged tissue preservation, but might have side effects. For instance, increased radical oxygen species or capillary endothelial damage. OBJECTIVE: To assess ultra-morphological muscle damage during 36-hour ECP of porcine musculocutaneous flaps, hypothesizing that it would delay the onset of damage compared to static cold storage (SCS). METHODS: Bilateral flaps were retrieved from three Dutch Landrace pigs. Three flaps were preserved for 36 hours by hypothermic storage 4-6°C (control group) and three flaps by ECP with cooled University of Wisconsin solution. Muscle biopsies were taken at 0 h, 12 h …and 36 h and assessed with transmission electron microscopy. RESULTS: Muscle architecture was best preserved by ECP, with a delayed onset and decreased severity of muscle damage. After 36 hours, damage was two-fold lower in ECP-flaps compared to SCS-flaps. Myofibril architecture was best preserved. Mitochondria were greatly preserved with swelling being the most prominent feature. Capillaries were moderately but differently damaged during ECP, with focal endothelial thinning as opposed to luminal obstruction in SCS-preserved flaps. CONCLUSIONS: This experiment described favourable cellular preservation of skeletal muscle flaps during ECP compared to SCS. Results showed less severe ultra-morphological damage and a later onset of damage. Show more

Keywords: Ischemia-reperfusion injury, ex-vivo preservation, machine perfusion, organelles, hypothermic storage

DOI: 10.3233/CH-211262

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2022

Authors: Binneboessel, Stephan | Bruno, Raphael Romano | Wernly, Bernhard | Masyuk, Maryna | Flaatten, Hans | Fjølner, Jesper | Wolff, Georg | Kelm, Malte | Beil, Michael | Sviri, Sigal | Szczeklik, Wojciech | Leaver, Susannah | De Lange, Dylan W. | Guidet, Bertrand | Jung, Christian

Article Type: Research Article

Abstract: BACKGROUND: COVID-19 is associated with cytokine release in critical disease states. Thus, cytokine absorption has been proposed as a therapeutic option. This study investigated the influence of cytokine absorption on mortality in old critical patients with COVID-19 and renal failure admitted to intensive care units (ICU). METHODS: This retrospective analysis of a prospective international observation study (the COVIP study) analysed ICU patients≥70 years with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, clinical frailty scale (CFS), ICU therapy details including renal replacement therapy (RRT) with/without cytokine absorption were collected. The cytokine absorption group was compared to patients …receiving RRT without cytokine absorption RESULTS: Among 3927 patients, 503 received RRT; among them 47 patients were treated with cytokine absorption. Mortality rates were high in both groups with increased rates in the cytokine group for ICU mortality and 30-day mortality, but not for 3-month mortality. Logistic regression analysis indicated that SOFA-score, but not cytokine absorption was associated with mortality. CONCLUSIONS: Critical COVID-19 patients with renal failure treated with cytokine absorption showed higher short term mortality rates when compared to patients with renal replacement therapy alone. Mortality is associated with disease severity, but not cytokine absorption in a multivariate analysis. Show more

Keywords: Cytokine absorption, COVID-19, critically ill, ICU, mortality, srenal replacement therapy

DOI: 10.3233/CH-221579

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Bai, Chen | Wang, Jiangang | Li, Jingxing

Article Type: Research Article

Abstract: BACKGROUND: Atherosclerosis (AS) is defined as a chronic inflammatory disorder underly the pathogenesis of cardiovascular diseases (CVDs). Endothelial pyroptosis is associated with AS-like diseases and other CVDs. OBJECTIVE: This work was designed to expound on the effect of GATA-binding protein 1 (GATA1) on pyroptosis of human coronary artery endothelial cells (HCAECs) in AS. METHODS: HCAECs were treated with oxidized-low density lipoprotein (ox-LDL) to establish HCAEC injury models. Plasmids for overexpressing GATA1 or silencing retinoic acid-related orphan receptor α (RORα) were transfected into HCAECs. Thereafter, the mRNA levels of GATA1 and RORα in HCAECs were detected using …real-time quantitative polymerase chain reaction. HCAEC viability was examined using the cell counting kit-8 method. The levels of pyroptosis-related proteins NOD-like receptor protein 3 (NLRP3), cleaved-Caspase-1, N-terminal of gasdermin D (GSDMD-N), and pyroptosis-related inflammatory cytokines interleukin (IL)-1β and IL-18 were determined using Western blot and enzyme-linked immunosorbent assays, respectively. The targeting relationship between GATA1 and RORα was verified using the chromatin-immunoprecipitation assay. Then, the rescue experiment was conducted to explore the effect of RORα on pyroptosis of ox-LDL-treated HCAECs. RESULTS: In ox-LDL-treated HCAECs, GATA1 and RORα expressions were decreased, HCAEC viability was reduced, and the levels of NLRP3, cleaved-Caspase1, GSDMD-N, IL-1β, and IL-18 were elevated. GATA1 overexpression increased HCAEC viability and attenuated pyroptosis. GATA1 bound to the RORα promoter region to stimulate RORα transcription, and RORα suppression facilitated ox-LDL-induced pyroptosis of HCAECs. CONCLUSIONS: GATA1 activated RORα transcription and therefore limited pyroptosis of ox-LDL-treated HCAECs. Show more

Keywords: GATA1, RORα, HCAEC, ox-LDL, pyroptosis, NLRP3, GSDMD-N, cleaved-Caspase-1

DOI: 10.3233/CH-221536

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Kaiser, Ulrich | Herr, Wolfgang | Greiner, Babara | Stroszczynski, Christian | Jung, Ernst Michael

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to evaluate a new W-Lan-supported ultrasound mobile technology for the diagnosis of vascular peripheral thrombosis. MATERIAL and METHODS: Fifty patients were examined by an experienced reference sonographer using high-end technology and a W-Lan supported device (VScan Air) to evaluate its diagnostic capabilities for peripheral thrombosis. RESULTS: Fifty patients were examined (age, 25–88 years; male, n  = 27, female n  = 23). Thromboses were diagnosed in the neck (n  = 1), upper leg (n  = 7), lower leg (n  = 49), and muscle veins (n  = 25). VScan Air technique also allows the diagnosis of circumscribed deep vein thrombosis …with a sufficient diagnostic certainty. Moreover, for superficial thrombi that can be well-delineated, a maximum image quality is possible compared to high-end technology. CONCLUSION: The mobile VScan technology opens up new possibilities for near-patient and location-independent imaging in cases of deep vein thrombosis. Show more

Keywords: Deep vein thrombosis, mobile ultrasound, peripheral thrombosis, VScan Air

DOI: 10.3233/CH-221598

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2022

Authors: Li, Chunxiao | Zhang, Huili | Chen, Jing | Shao, Sihui | Li, Xin | Yao, Minghua | Zheng, Yi | Wu, Rong | Shi, Jun

Article Type: Research Article

Abstract: OBJECTIVES: The purpose of our study is to present a method combining radiomics with deep learning and clinical data for improved differential diagnosis of sclerosing adenosis (SA)and breast cancer (BC). METHODS: A total of 97 patients with SA and 100 patients with BC were included in this study. The best model for classification was selected from among four different convolutional neural network (CNN) models, including Vgg16, Resnet18, Resnet50, and Desenet121. The intra-/inter-class correlation coefficient and least absolute shrinkage and selection operator method were used for radiomics feature selection. The clinical features selected were patient age and nodule size. …The overall accuracy, sensitivity, specificity, Youden index, positive predictive value, negative predictive value, and area under curve (AUC) value were calculated for comparison of diagnostic efficacy. RESULTS: All the CNN models combined with radiomics and clinical data were significantly superior to CNN models only. The Desenet121+radiomics+clinical data model showed the best classification performance with an accuracy of 86.80%, sensitivity of 87.60%, specificity of 86.20% and AUC of 0.915, which was better than that of the CNN model only, which had an accuracy of 85.23%, sensitivity of 85.48%, specificity of 85.02%, and AUC of 0.870. In comparison, the diagnostic accuracy, sensitivity, specificity, and AUC value for breast radiologists were 72.08%, 100%, 43.30%, and 0.716, respectively. CONCLUSIONS: A combination of the CNN-radiomics model and clinical data could be a helpful auxiliary diagnostic tool for distinguishing between SA and BC. Show more

Keywords: Deep learning, radiomics, breast cancer, sclerosing adenosis

DOI: 10.3233/CH-221608

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Glazkov, A.A. | Ulbashev, D.S. | Borshchev, G.G. | Pulin, A.A. | Glazkova, P.A. | Kulikov, D.A.

Article Type: Research Article

Abstract: BACKGROUND: Endothelial dysfunction and microvascular disturbances are suggested to play a key role in higher morbidity and worse prognosis in patients with COVID-19 and cardiometabolic diseases. OBJECTIVE: Study was aimed to establish relationships between the skin microcirculation parameters and various clinical and laboratory indicators. METHODS: The study included 18 patients with moderate disease according to WHO criteria. Skin microcirculation measurements were performed by laser Doppler flowmetry using a heating test on the hairy skin of the right forearm. RESULTS: Baseline perfusion only correlated with C-reactive protein (Rs = 0.5, p  = 0.034). Microcirculation indices characterising the development …of hyperaemia during the first minute of heating (LTH1 and AUC60 ) showed significant correlations (Rs from 0.48 to 0.67, p  <  0.05) with indices of general blood analysis and blood coagulation (fibrinogen, D-dimer, haemoglobin, erythrocyte count and haematocrit). Indexes characterising the dynamics of hyperaemia development over longer time intervals showed correlation with the glomerular filtration rate (Rs = 0.6, p  = 0.009). CONCLUSION: Known COVID-19 risk factors (haemorheological parameters, age) are correlated with the microvascular reactivity to heating in patients with COVID 19. We suggest that, prospectively, the method of laser Doppler flowmetry could be used for non-invasive instrumental assessment of microcirculatory disorders in patients with COVID-19. Show more

Keywords: COVID-19, microcirculation, local thermal hyperaemia, Laser Doppler flowmetry, haemorheology

DOI: 10.3233/CH-221431

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Zlojutro, Biljana | Jandric, Milka | Momcicevic, Danica | Dragic, Sasa | Kovacevic, Tijana | Djajic, Vlado | Stojiljkovic, Milos | Skrbic, Ranko | Djuric, Dragan | Kovacevic, Pedja

Article Type: Research Article

Abstract: INTRODUCTION: This study was created to analyze dynamic alterations in coagulation, hematological and biochemical parameters and their association with mortality of COVID-19 patients. To identify the most sensitive biomarkers as predictors of mortality more research is required. METHODS: The present study was a prospective, one-year-long observational study conducted on all critically ill, COVID–19 patients with respiratory failure. The following data were collected: demographic and clinical characteristics of the study population, comorbidities, coagulation, biochemical and hematological parameters. The primary outcome was the proportion of patients who died. RESULTS: 91 patients with median age 60 (50–67), 76.9% male, …met the acute respiratory distress syndrome criteria. It was tested whether dynamic change (delta-Δ) of parameters that were found to be predictors of mortality is independently associated with poor outcome. Adjusted (multivariate) analysis was used, where tested parameters were corrected for basic and clinical patients characteristics. The only inflammatory parameter which dynamic change had statistically significant odds ratio was ΔCRP (p  < 0.005), while among coagulation parameters statistically significant OR was found for Δ fibrinogen (p  < 0.005) in predicting mortality. CONCLUSION: Monitoring of coagulation, hematological and biochemical parameters abnormalities and their dynamical changes can potentially improve management and predict mortality in critically ill COVID –19 patients. Show more

Keywords: COVID–19, crtically ill, cogulation, biochemical, hematological, mortality

DOI: 10.3233/CH-221583

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Hahn, Robert G.

Article Type: Research Article

Abstract: BACKGROUND: “Interstitial washdown” is an edema-preventing mechanism that implies a greater redistribution of interstitial albumin occurs whenever the capillary filtration is increased. OBJECTIVE: To study the effect of interstitial washdown on fluid distribution in normovolemic and hypovolemic volunteers. METHODS: Capillary filtration was increased by infusing 25 mL/kg Ringer’s acetate intravenously over 30 min 10 male just after withdrawal of 0, 450, and 900 mL of blood. Population volume kinetic analysis was used to assess the effects of washdown and hemorrhage on fluid distribution, using the difference in plasma dilution based on hemoglobin and albumin as biomarker of washdown. …RESULTS: Blood withdrawal during 10–15 min recruited 100–150 mL of fluid of high albumin content to the plasma, which was probably lymph. The albumin recruitment was temporarily reduced during the fluid loading but increased from 40 min post-infusion and was then greater when preceded by hemorrhage. Simulations suggested that interstitial washdown decreased the extravascular fluid volume by 200 mL over 3 h. The plasma volume and urinary excretion both increased by approximately half this amount. CONCLUSIONS: Blood loss without hypotension probably recruited lymph to the plasma, but interstitial washdown played no major role in determining the distribution of crystalloid fluid after hemorrhage. Show more

Keywords: Crystalloid solution, pharmacokinetics, extracellular space, physiology, lymphatic flow, pharmacokinetics

DOI: 10.3233/CH-221531

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Watson, Oliver | Zaldua, Jun-Cezar | Pillai, Suresh | Whitley, Janet | Howard, Matthew | Lawrence, Matthew | Hawkins, Karl | Morris, Keith | Evans, Phillip Adrian

Article Type: Research Article

Abstract: BACKGROUND: A significant degree of mortality and morbidity in Covid-19 is through thromboembolic complications, only partially mitigated by anticoagulant therapy. Reliable markers of infection severity are not fully established. OBJECTIVES: This study investigated whether visco-elastic biomarkers predict disease severity on presentation to the Emergency Department (ED) and how they measure response to anticoagulation METHODS: Patients testing positive for Covid-19 at a large University Teaching Hospital ED were recruited at presentation. Multiple blood samples were taken throughout hospital admission to monitor disease progression with end outcome recorded. Visco-elastic markers, fractal dimension (d f ) and Time …to Gel Point (TGP) which measure the properties of the incipient clot were compared in patients with and without anticoagulation by Low Molecular Weight Heparin (LMWH). RESULTS: TGP and d f did not predict severity of infection with Covid-19. Although LMWH prolonged TGP, there was no change in d f indicating LMWH did not change clot microstructure. CONCLUSIONS: Therapeutic efficacy of LMWH appears blunted in Covid-19 infection. This may be due to the inflammatory state creating a resistance to LMWH activity, which may explain why LMWH appears less effective in Covid-19 compared to other disease states. Covid-19 was not predicted by visco-elastic testing at the time of ED presentation. Show more

Keywords: Covid-19, coagulopathy, visco-elastic testing, anticoagulation, Heparin resistance

DOI: 10.3233/CH-221635

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Kaiser, Ulrich | Dropco, Ivor | Reuthner, Kathrin | Ertl, Michael | Schlitt, Hans Jürgen | Herr, Wolfgang | Stroszczynski, Christian | Jung, Ernst Michael

Article Type: Research Article

Abstract: OBJECTIVE: The study aim was to investigate the use of a novel device, the Vscan Air™, for rapidly and effectively performing ultrasound in student teaching during the COVID-19 pandemic. MATERIAL AND METHODS: As part of the ultrasound practical course with integrated hands-on activity required by the regular medical curriculum, 100 medical students were instructed in the use of the Vscan Air™, including duplex mode. They then evaluated the quality of the ultrasound images obtained by the Vscan Air™ from previously selected organs. RESULTS: 100 students were interviewed (female n  = 68, male n  = 32; age >18 years …n  = 100). The rated image quality never fell below a mean of 3 for the examined organs and portal vein flow (liver 4,58; spleen 3,99; kidneys 4,29; aorta 4,16; Douglas/rectovesical space 4,14; portal vein 4,43; pancreas 3,53; Focused Assessment with Sonography for Trauma 4,38). Scores below 3 were found sporadically in ultrasounds of the spleen (n  = 4), kidneys (n  = 3), Douglas/rectovesical space (n  = 2), and pancreas (n  = 15). The liver was rated the lowest for 59 ratings. The portal vein was evaluated in 68 cases. The hepatic artery and hepatic veins could be also visualized in all 68 examinations. The aorta was evaluated in 62 cases. CONCLUSION: The Vscan Air™ technology offered adequate image quality and provided a new, fast and patient-oriented technique to support continuous ultrasound examinations and education of students, especially during a pandemic. Particularly noteworthy is the uncomplicated compliance with the required high level of hygiene. Show more

Keywords: VScan Air, mobile ultrasound, ultrasound, student teaching

DOI: 10.3233/CH-229104

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Anker, Alexandra M. | Lenhard, Jasmin | Klein, Silvan M. | Felthaus, Oliver | Prantl, Lukas | Ruewe, Marc

Article Type: Research Article

Abstract: BACKGROUND: Recent studies have demonstrated that local application of corticosteroids reduces wound exudation following abdominoplasty and other reconstructive surgical procedures. On the other hand, corticosteroids might provoke wound healing disturbances due to their immunosuppressive effects. OBJECTIVE: The main objective of this study was to gain further information about the impact of the corticosteroid triamcinolone on cell migration in abdominoplasty patients. METHODS: An in-vitro scratch assay wound healing model was applied to observe cell migration of fibroblasts cultured with nutrient medium containing human seroma aspirate±triamcinolone. RESULTS: There were no significant differences regarding cell migration …when fibroblasts were incubated with triamcinolone + seroma containing culture medium compared to seroma containing culture medium without triamcinolone. CONCLUSIONS: The performed in-vitro study suggests that triamcinolone does not decelerate fibroblast cell migration which is considered as a surrogate of wound healing. Show more

Keywords: Cell migration, fibroblasts, corticosteroids, triamcinolone, scratch assay

DOI: 10.3233/CH-229106

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2022

Authors: Brebant, V. | Lemonnier, L. | Georgieva, M. | Anker, A. | Heine, N. | Seitz, S. | Frank, K. | Prantl, L. | Eigenberger, A.

Article Type: Research Article

Abstract: BACKGROUND: Reconstructive surgery is established as a standard treatment option after mastectomy due to cancer. It is crucial to patients to achieve a natural and symmetric looking breast through reconstruction. Anthropometric measurements are used to assess the objective symmetry of the breast, which are prone to errors and difficult to reproduce. OBJECTIVE: The aim of this work is to validate breast volumetry using three-dimensional surface imaging. METHODS: We compared preoperatively analog and digitally evaluated volume of the breast with our gold standard, direct water displacement measurement of the mastectomy specimen. We examined 34 breast specimens in …total. RESULTS: Each measurement method (Breast Sculptor, VAM, Breast-V) for breast volume/mass determination demonstrates acceptable agreement ranges when compared with resected volumes and masses. The strongest volumetry instrument is Breast Sculptor (digital), the weakest is Breast-V (analog). CONCLUSIONS: 3D surface imaging is a quick, effective, and convenient method to evaluate breast shape and volume. The accuracy, reproducibility, and reliability of 3D surface imaging were comparable with MRI in our study. This takes us a step closer to the long-term goal of establishing robust instruments to plan breast reconstructive surgery, achieve better surgical results, and contribute to quality assurance in breast surgery. Show more

Keywords: Breast reconstruction, breast cancer, 3D imaging, breast surgery, volumetry, anthropometry

DOI: 10.3233/CH-229101

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Braune, S. | Krüger-Genge, A. | Köhler, S. | Küpper, J.-H. | Jung, F.

Article Type: Research Article

DOI: 10.3233/CH-229103

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2022

Authors: Rother, D. | Gehron, J. | Brenck, F. | Hudel, H. | Böning, A. | Wenzel, F.

Article Type: Research Article

Abstract: INTRODUCTION: COVID-19 causes a considerable degradation of pulmonary function to the point of an acute respiratory distress syndrome (ARDS). Over the course of the disease the gas exchange capability of the lung can get impaired to such an extent that extracorporeal membrane oxygenation (ECMO) is needed as a life-saving intervention. In patients COVID-19 as well as ECMO may cause severe coagulopathies which manifest themselves in micro and macro thrombosis. Previous studies established D-dimers as a marker for critical thrombosis of the ECMO system while on admission increased D-dimers are associated with a higher mortality in COIVD-19 patients. It is therefore …crucial to determine if COVID-19 poses an increased risk of early thrombosis of the vital ECMO system. METHODS: 40 patients who required ECMO support were enrolled in a retrospective analysis and assigned into 2 groups. The COVID group consist of 20 COVID-19 patients who required ECMO support (n  = 20), whereas 20 ECMO patients without COVID-19 were assigned to the control group. D-dimers, fibrinogen, antithrombin III (AT III), lactate dehydrogenase (LDH) and platelet count were analysed using locally weighted scatterplot smoothing and MANOVAs. RESULTS: The analysis of both groups shows highly significant differences in the dynamics of hemostasis. The increase in D-dimers that is associated with thrombosis of the ECMO systems occurs in COVID-19 patients around 2 days earlier (p  = 2,8115 10–11 ) while fibrinogen is consumed steadily. In the control group fibrinogen levels increase rapidly after ten days with a plateau phase of around five days (p  = 1,407 10–3 )  . Both groups experience a rapid increase in AT III after start of support by ECMO (p  = 5,96 10–15 ). In the COVID group platelet count decreased from 210 giga/l to 130 giga/l within eight days, while in the same time span in the control group platelets decreased from 180 giga/l to 105 giga/l (p  = 1,1 10–15 ). In both groups a marked increase in LDH beyond 5000 U/l occurs (p  = 3,0865 10–15 ). CONCLUSION: The early increase in D-dimers and decrease in fibrinogen suggests that COVID-19 patients bear an increased risk of early thrombosis of the ECMO system compared to other diseases treated with ECMO. Additionally, the control group shows signs of severe inflammation 10 days after the start of ECMO which were absent in COVID-19 patients. Show more

DOI: 10.3233/CH-229105

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Koutsiaris, Aristotle G. | Batis, Vasilios | Liakopoulou, Georgia | Tachmitzi, Sophia V. | Detorakis, Efstathios T. | Tsironi, Evangelia E.

Article Type: Research Article

Abstract: Optical Coherence Tomography Angiography (OCTA) is a relatively new imaging technique in ophthalmology for the visualization of the retinal microcirculation and other tissues of the human eye. This review paper aims to describe the basic definitions and principles of OCT and OCTA in the most straightforward possible language without complex mathematical and engineering analysis. This is done to help health professionals of various disciplines improve their understanding of OCTA and design further clinical research more efficiently. First, the basic technical principles of OCT and OCTA and related terminology are described. Then, a list of OCTA advantages and disadvantages, with a …special reference to blood flow quantification limitations. Finally, an updated list of the basic hardware and software specifications of some of the commercially available OCTA devices is presented. Show more

Keywords: OCTA, eye, basic principles, advantages, disadvantages, pros and cons, microvessels, blood flow, device specifications

DOI: 10.3233/CH-221634

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-25, 2022

Authors: Jung, F. | Lamby, P. | Prantl, L. | Wiggermann, P. | Jung, E.M. | Krüger-Genge, A. | Franke, R.P.

Article Type: Research Article

Abstract:  Iodinated contrast media (ICM) are widely used for diagnostic and interventional procedures in radiology and cardiology. Ideally, they should not interact with blood cells or vascular wall cells to avoid deteriorations of the blood circulation. However, it is well known that ICM can affect erythrocytes as well as endothelial cells which consequently might perturb especially the microcirculation. In former studies the influence of two ICM (iodixanol versus iopromide) on the vascular system, the development of blood stasis, on changes in renal resistive index (RRI) and vascular diameters, and on the post-mortem distribution of iodine as marker for ICM in the …explanted kidneys was examined. The modus of ICM application into the supra-renal aorta followed the regime in interventional cardiology, so that 10 bolus injections were administered at steady intervals (iopromide 4,32 ml / iodixanol 5 ml) accompanied by infusion of 500 ml isotonic NaCl-solution. In the present study, the post-mortem X-ray analysis revealed that there were no differences in iodine content in the regions of the mid-cortex and the medullo-pelvic transition zone of the kidneys after application of both ICM. Remarkable differences, however, were found in the region of the capsule-near cortex, where the application of iopromide led to a significantly lower iodine content in the microcirculation. This is in good agreement with former studies, in which a maldistribution in this area, presumably due to a decrease in arteriolar inflow as a result of stasis/occlusion was shown. Show more

Keywords: Iodinated contrast media, iodixanol, iopromide, kidney

DOI: 10.3233/CH-229102

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2022

Authors: Wagner, Marie | Anzinger, Eveline | Hey, Florian | Reiter, Karl | Wermelt, Julius Z. | Pastor-Villaescusa, Belén | Genzel-Boroviczény, Orsolya | Nussbaum, Claudia

Article Type: Research Article

Abstract: BACKGROUND: Monitoring of the macrocirculation during surgery provides limited information on the quality of organ perfusion. OBJECTIVE: We investigated the feasibility of perioperative microcirculatory measurements in children. METHODS: Sublingual microvessels were visualized by handheld videomicroscopy in 11 children (19 mo – 10 yrs) undergoing surgery > 120 min at four time points: T0) after induction of anesthesia; T1) before end of anesthesia, T2) 6 h post surgery and T3) 24 h post surgery. RESULTS: Measurements were feasible in all children at T0 and T1. At T2 and T3, imaging was restricted to 6 and 4 infants, respectively, due to …respiratory compromise and missing cooperation. The capillary density was reduced at T1 compared to T0 (8.1 mm/mm2 [4.0-17.0] vs. 10.6 mm/mm2 [5.1-19.3]; p  = 0.01), and inversely related to norepinephrine dose (Pearson r  = -0.65; p  = 0.04). Microvascular flow and serum glycocalyx makers Syndecan-1 and Hyaluronan increased significantly from T0 to T1. CONCLUSION: Perioperative microcirculatory monitoring in children requires a high amount of personal and logistic resources still limiting its routine use. Major surgery is associated with microvascular alterations and glycocalyx perturbation. The possible consequences on patient outcome need further evaluation. Efforts should concentrate on the development of next generation devices designed to facilitate microcirculatory monitoring in children. Show more

Keywords: Microcirculation, child, surgery, microvascular density, glycocalyx, blood flow

DOI: 10.3233/CH-221617

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2022

Authors: Lim, Soyeon | Kim, Sang Woo | Kim, Il-Kwon | Song, Byeong-Wook | Lee, Seahyoung

Article Type: Research Article

Abstract: Organ-on-a-chip (OOAC) has attracted great attention during the last decade as a revolutionary alternative to conventional animal models. This cutting-edge technology has also brought constructive changes to the field of cardiovascular research. The cardiovascular system, especially the heart as a well-protected vital organ, is virtually impossible to replicate in vitro with conventional approaches. This made scientists assume that they needed to use animal models for cardiovascular research. However, the frequent failure of animal models to correctly reflect the native cardiovascular system necessitated a search for alternative platforms for preclinical studies. Hence, as a promising alternative to conventional animal models, …OOAC technology is being actively developed and tested in a wide range of biomedical fields, including cardiovascular research. Therefore, in this review, the current literature on the use of OOACs for cardiovascular research is presented with a focus on the basis for using OOACs, and what has been specifically achieved by using OOACs is also discussed. By providing an overview of the current status of OOACs in cardiovascular research and its future perspectives, we hope that this review can help to develop better and optimized research strategies for cardiovascular diseases (CVDs) as well as identify novel applications of OOACs in the near future. Show more

DOI: 10.3233/CH-221428

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-25, 2022

Authors: Chen, Min | Shi, Siren | Zhao, Jianyong | Pan, Qin | Huang, Changjun | Shen, Quanwei | Liu, Zhaohui

Article Type: Research Article

Abstract: BACKGROUND: Propofol is an anesthetic agent and can impede the progression of human diseases. Circular RNA (circRNA) circ_0003645 has been identified to promote the development of atherosclerosis (AS). This study aimed at the functional mechanism of propofol and circ_0003645 in AS. METHODS: AS cell model was established by treatment of oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs). Cell viability or apoptosis detection was performed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Circ_0003645, microRNA-149-3p (miR-149-3p) and tumor necrosis factor receptor-associated factor 7 (TRAF7) levels were determined by the quantitative real-time polymerase chain reaction …(qRT-PCR). Inflammatory cytokines were examined using enzyme-linked immunosorbent assay (ELISA). Protein analysis was conducted by western blot. The interaction of miR-149-3p and circ_0003645 or TRAF7 was analyzed using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Treatment of ox-LDL inhibited cell viability and enhanced apoptosis in HUVECs to establish the AS cell model. Propofol protected against cell viability inhibition and apoptosis promotion in AS cell model. Circ_0003645 expression was downregulated by propofol in AS cell model. Propofol alleviated cell apoptosis and inflammation by decreasing the circ_0003645 level. Circ_0003645 targeted miR-149-3p, and circ_0003645/miR-149-3p axis was involved in the functional regulation of propofol. TRAF7 was the target of miR-149-3p. Inhibition of miR-149-3p affected the function of propofol by upregulating the TRAF7 expression. Circ_0003645 sponged miR-149-3p to induce the upregulation of TRAF7 following propofol treatment. CONCLUSION: It has been suggested that propofol acted as an inhibitor against the ox-LDL-induced cell injury by the circ_0003645/miR-149-3p/TRAF7 axis. Show more

Keywords: Propofol, atherosclerosis, circ_0003645, miR-149-3p, TRAF7

DOI: 10.3233/CH-221437

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2022

Authors: Jian, Zheng-Wei | Zhang, Xiao-Ming | Huang, Guan-Shen

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the clinical value of platelet and inflammatory factor activation in vascular endothelial injury in hypertension. METHODS: A total of 120 hypertension patients diagnosed in our hospital from December 2019 to June 2021 were enrolled as study objects (Hypertension group); besides, another cohort of 60 healthy people undergoing physical examination at the same period were recruited as the controls (Control group). Next, the baseline clinical characteristics of subjects in the two groups were recorded and compared. Specifically, a hematology analyzer was adopt for detecting the mean platelet volume (MPV), platelet distribution width (PDW) and platelet hematocrit …(PCT); ELISA for the level of IL-6, IL-8 and TNF-α ; PHILIPS EPIQ 7 C (a device assessing endothelial vasodilator function in a non-invasive fashion) for reactive hyperemia index (RHI); univariate and multivariate regression analysis for risk factors triggering endothelial dysfunction; and Spearman correlation analysis for the correlation of platelet activation indicators and inflammatory factor level with vascular endothelial function. RESULTS: Compared with the Control group, the patients in the Hypertension group exhibited higher levels of MPV, PDW, PCT, inflammatory factors (IL-6, IL-8 and TNF-α ) and lower RHI. Moreover, Spearman correlation analysis showed a significant negative correlation of MPV, PDW, PCT, IL-6, IL-8 and TNF-α level with RHI level. In addition, univariate and multivariate regression analysis presented that MPV, PCT, IL-8 and TNF-α were risk factors for vascular endothelial dysfunction. CONCLUSION: The activation of platelet and inflammatory factor is closely related to vascular endothelial function injury in patients with hypertension. To be specifically, platelet and inflammatory factor activation can effectively reflect the vascular endothelial function injury in patients with hypertension and has high clinical value. Show more

Keywords: Platelet activation, inflammatory factors, hypertension, vascular endothelial injury, clinical value

DOI: 10.3233/CH-221638

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Antonova, Nadia | Khristov, Khristo | Alexandrova, Anika | Muravyov, Alexei | Velcheva, Irena

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Microfluidics is a useful tool for investigating blood microrheology. The study aimed to present the development of a microfluidic device for assessing the microrheological properties of blood cells’ suspensions and its application in patients with T2DM. METHODS: A new microfluidic device was elaborated, connected to a system, including a microscope with a digital camera, a pump with a manometer and a computer with specially developed software. Blood cells’ suspensions were investigated in a microchamber between two parallel optical slides within a 100μm distance. The motion of the blood cells in the microchamber was observed by …the microscope and it was recorded and visualized by a digital camera. A method for evaluating the deformability of blood cells and a device for its implementation were used [1 ]. RESULTS: The pressure and flow rate ranges in the microfluidic device were specified by model suspensions of beta-ferroxy-hydroxide and red blood cells (RBC) suspensions. The pressure changes, realized by a pump (micropipette), connected to a manometer were established and the corresponding shear rates in the microfluidic device were determined. Data about the blood microrheological properties like RBC aggregation and deformability, leukocyte adhesion from a group of healthy volunteers and from patients with type 2 diabetes mellitus (T2DM) were obtained. CONCLUSIONS: The developed device and experimental system is a promising tool for the study of blood microrheology. Show more

Keywords: Microfluidic device, methodology, microrheology, red blood cell (RBC) deformability and aggregation, leukocyte adhesion, type 2 diabetes mellitus (T2DM)

DOI: 10.3233/CH-221631

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2022

Authors: Ptaszek, Bartłomiej | Podsiadło, Szymon | Teległów, Aneta

Article Type: Research Article

Abstract: OBJECTIVE: assessment of the effect of a series of 20 whole-body cryotherapy sessions on the morphological and rheological indicators of blood in healthy people. METHODS: The experimental group consisted of 15 women and 15 men who underwent a series of whole-body cryotherapy treatments. The control group consisted of 15 women and 15 men - without intervention. For the analysis of blood biochemical parameters, venous blood was collected twice: Study 1: on the day of the commencement of whole body cryotherapy / from the control group; and Study 2: after a series of 20 cryotherapy sessions / from the …control group (4 weeks). RESULTS: After whole-body cryotherapy a statistically significant decrease in RBC, HGB, HCT, MCV, EI 0.30 and an increase in MCHC and EI 2.19–60.30 were observed in women, as well as a decrease in MCV, MCH, AI and an increase in PLT, EI 0.30–60.30, AMP, T1/2 in men. CONCLUSIONS: The use of whole-body cryotherapy causes changes in blood counts in various directions and has a positive effect on the rheological properties of blood in women and men - it increases the elongation index and reduces the aggregation index. Show more

Keywords: Whole-body cryotherapy, blood morphology, blood rheology, red blood cell deformability, red blood cell aggregation

DOI: 10.3233/CH-221658

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2022

Authors: Schramm, D. | Wohlgemuth, W.A. | Guntau, M. | Wieprecht, M. | Deistung, A. | Bidakov, O. | Wildgruber, M. | Brill, R. | Cucuruz, B.

Article Type: Research Article

Abstract: BACKGROUND: Venous malformations tend to retain their slow-flow behavior, even in progressive disease or regression following therapy. OBJECTIVE: The aim of this study is to analyze the development of acquired hemodynamic relevant arterio-venous fistulae in patients with slow-flow malformations. METHODS: This study is a retrospective analysis based on a consecutive local registry at a tertiary care Interdisciplinary Center for Vascular Anomalies. Patients with venous malformations and development of secondary arterio-venous fistulae were included. Indications for therapy of the vascular malformation were based on patients’ symptoms and complications. The following endpoints were of clinical interest and were …assessed: origin of development of arteriovenous fistula, development of secondary comorbidities as a result of the vascular malformation. For analysis we focused on descriptive statistics. RESULTS: Out of 1213 consecutive patients with vascular malformations, in 6 patients perfusion changed from slow flow to arterio-venous fast-flow patterns. Four patients developed the fistula after local trauma in the area of the malformation, the other 2 patients developed the fistula due to progression of the disease and recurrent thrombophlebitis. These 2 patients had no trauma or interventions at the time of arterio-venous fistula development. CONCLUSIONS: Acquired arterio-venous fast-flow fistula in patients with slow flow vascular malformation is very rare and might be a result of local trauma or the progression of the disease with recurrent thrombophlebitis. Specific evidence-based treatment options for these patients do not exist. Show more

Keywords: Congenital vascular malformation, arterio-venous fistula, slow flow malformation, fast flow malformation

DOI: 10.3233/CH-221610

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Ebrahimi, Zahra | Farsinejad, Alireza | Mohammadi, Mohammad Hossein | Ahmadizad, Sajad

Article Type: Research Article

Abstract: BACKGROUND: Resistance exercise induces thrombocytosis and increases platelet activation and function. These changes might be related to exercise variables including exercise intensity and type. OBJECTIVE: We compared the effects of traditional resistance exercise (TRE) and circuit resistance exercise (CRE) on cellular markers of platelet activation and function. METHODS: In this crossover study ten healthy male (mean±SD: age, 25.6±2.4 years) subjects performed TRE encompassed 3 sets of 10 repetitions at 100% of 10-RM (10 repetition maximum) for 6 exercises, and CRE protocols included 3 sets of 10 repetitions at 100% of 10-RM for all 6 exercises consecutively, …in two separate weeks. To measure platelet indices, PAC1, CD41a, CD42b and CD62P three blood samples were taken before, immediately after exercise, and after 30 min recovery. RESULTS: Lactate concentration, blood pressure, platelet count (PLT), and mean platelet volume (MPV) were significantly (p  <  0.05) increased following both resistance exercise trials. Significant increases in PAC1, and CD62P; and significant reductions for CD42b and CD41a were detected following both REs (p  <  0.05). However, changes in PAC1 and CD62P were significantly different between the two protocols (p  <  0.05), with higher increases detected following CRE. CONCLUSIONS: Acute RE increases platelet indices and platelet activation; and that CRE results in higher platelet activation than TRE, probably due to exercise-induced increases in shear stress. Show more

Keywords: Resistance exercise, weight training, platelet activation, P-selectin, PAC1

DOI: 10.3233/CH-221603

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Lehmann, Christian | Zhou, Juan

Article Type: Research Article

Abstract: Cannabinoids play critical roles in human pathophysiology through the cannabinoid (CB) receptors and non-CB receptors on variety of cells, tissues, and organs. Microvasculature with the inside bloodstream containing the plasmatic and cellular components exerts multiple functions in maintaining tissue and organ physiology through microcirculation. This review focusses on the impact of cannabinoids on the microvasculature, including mechanisms mediated by both CB receptor-related pathways and CB receptor-independent pathways.

Keywords: Cannabinoids, microcirculation, cannabinoid receptors, smooth muscle cells

DOI: 10.3233/CH-221677

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2022

Authors: Chen, Zhe | Qiu, Zhong-Xian | Guo, Dong-Ming | Wang, Jia-Jia | Guo, Hai-Ting | Su, Hong-Hui | Dai, Zhuo-Zhi | Zhai, Yu-Xia

Article Type: Research Article

Abstract: BACKGROUND: The inadequacy samples caused by the internal characteristic structure of thyroid nodules are difficult to be solved. OBJECTIVE: To evaluate the ultrasound features affecting the sample adequacy after fine-needle aspiration (FNA) of thyroid nodules with different risk stratification. METHODS: 592 thyroid nodules that underwent ultrasound-guided FNA were included in this retrospective study. The sample obtained by FNA were classified as inadequacy and adequacy according to the cytopathological results. Ultrasound features (ie., size, position, cystic predominance, composition, echo, shape, margin, and superficial annular calcification status) of the nodules were recorded and compared between the inadequacy sample …group and adequacy sample group. RESULTS: Multiple logistic regression shows that preponderant cystic proportion (OR, 0.384; P  = 0.041), extremely hypoechogenicity and hypoechogenicity (OR, 6.349; P  = 0.006) were the independent influencing factors of inadequate samples after FNA in benign expected nodules. In addition, nodule size ≤10 mm (OR, 1.960; P  = 0.010) and superficially annular calcification (OR, 4.600; P  <  0.001) were independent influencing factors for inadequate samples after FNA in malignant expected nodules. CONCLUSION: The ultrasound features of hypoechogenicity or high cystic proportion in benign expected nodules and that of small size or annular calcification in malignant expected nodules were the risk factors for inadequacy samples by US-guided FNA. Show more

Keywords: Ultrasound features, thyroid nodule, fine-needle aspiration, inadequacy sample

DOI: 10.3233/CH-221659

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2023

Authors: Tazegul, Hatice | Ozen, Nur | Yildirim, Ahmet | Ulker, Pinar | Hadimioglu, Necmiye | Cakin, Ozlem | Yoldas, Sukran Burcak | Yilmaz, Murat | Cengiz, Melike

Article Type: Research Article

Abstract: BACKGROUND: Liver transplantation is a life-saving treatment in end-stage liver failure. Hemorheological features as blood fluidity and red blood cell aggregation may alter effective tissue perfusion, graft function and hemodynamic variables. OBJECTIVE: The aim of the study is to investigate effect of albumin infusion on red blood cell deformability and aggregation, blood viscosity and hemodynamics in liver transplant patients. METHODS: Seventeen live or cadaveric donors were included in this prospective study. Hemorheological and hemodynamic measurements were performed in order to evaluate the effects of albumin infusion in perioperative period. RESULTS: Erythrocyte aggregation was significantly …reduced 90 minutes after albumin infusion (p  <  0.01). Mean blood viscosity revealed significant decrease at 20 rpm and 50 rpm after 90 minutes of albumin infusion (p  <  0.05). Plasma viscosity decreased significantly compared to the value before albumin infusion at 20 rpm (p  <  0.05). Albumin replacement improved hemodynamic variables in patients with low blood pressure and cardiac index measurements (p  >  0.05). CONCLUSIONS: Human albumin infusion led to decrease in whole blood and plasma viscosities, red blood cell aggregation and induced blood pressure and cardiac index elevation in perioperative liver transplant patients. Determination of hemodynamic and hemorheological effects of human albumin replacement in various patient populations may serve beneficial clinical data. Show more

Keywords: Albumin, hemorheology, viscosity, aggregation, transplantation

DOI: 10.3233/CH-221473

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Wang, Kun | Dong, Yi | Han, Hong | Cao, Jiaying | Bao, Jingwen | Wang, Wen-Ping

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to evaluate the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) with a propagation map in evaluating the degree of hepatic fibrosis in patients with liver tumors before resection. METHODS AND MATERIALS: From January 2020 to April 2021, 128 patients with liver tumors were prospectively enrolled, including 20 benign liver tumors and 108 malignant liver tumors. 2D-SWE with a propagation map technology was used to measure the stiffness of liver parenchyma 2 cm away from the tumor. The median value of five measurements was used in this study. The stage of hepatic fibrosis was …graded in accordance with Scheuer standard. Spearman correlation was used to analyze the correlation between liver fibrosis stage and the liver stiffness. Univariate and multivariate linear regression analyses were used to determine significant affecting factors for liver stiffness value. The diagnostic performance of 2D-SWE with a propagation map in predicting fibrosis stage was evaluated by receiver operating characteristic curve analysis. RESULTS: The median liver stiffness value in patients with benign liver tumors was lower than that in patients with malignant liver tumors (6.0 kPa vs. 9.4 kPa, p  <  0.05). The median liver stiffness values in patients with primary liver cancer were higher than that in patients with benign liver tumors and other types of malignant liver tumors (9.6 kPa vs. 6.0 kPa, p  <  0.05). The liver stiffness measured by 2D-SWE was highly correlated with the fibrosis stage confirmed by postoperative pathology (r  = 0.834, p  <  0.05). For the liver stiffness value, PLT,TB,ALB and fibrosis stage are significantly associated with liver stiffness. The median liver stiffness values in stages S0–S4 of fibrosis were 6.0, 7.2, 8.0, 9.4, and 12.6 kPa, respectively. The areas under the ROC curve of S ≥1, S ≥2, S ≥3, and S  = 4 as predicted by SWE were 0.932, 0.945, 0.945, and 0.916, respectively. According to the Youden index, the optimal critical values for predicting fibrosis S ≥1, S ≥2, S ≥3, and S  = 4 were 6.8 (sensitivity of 89.69% and specificity of 93.55%), 7.5 (sensitivity of 87.50 % and specificity of 95.00 %), 8.3 (sensitivity of 87.14 % and specificity of 87.93 %) and 9.8 (sensitivity of 79.55 % and specificity of 86.90 %) kPa. CONCLUSION: 2D-SWE with a propagation map could noninvasively and accurately predict the staging of liver fibrosis in patients with liver tumors before resection. Show more

Keywords: Shear wave elastography, liver fibrosis, ultrasound, propagation map

DOI: 10.3233/CH-221511

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Yu, Mei-qin | Zhang, Li-li | Jiang, Li-ping | Zhou, Ai-yun

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is the most common malignant tumor in women. Early diagnosis of benign and malignant breast tumors is of great significance. OBJECTIVE: To retrospectively analyze the value of contrast-enhanced ultrasonography (CEUS) in the diagnosis of Breast Imaging-Reporting and Data System (BI-RADS) 4a breast lesions less than 2 cm in diameter. METHODS: CEUS was performed for 143 breast masses less than 2 cm in diameter that were diagnosed as BI-RADS 4a by ultrasound and reclassified. Considering pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of reclassified lesions …after CEUS for the diagnosis of benign and malignant masses were analyzed. RESULTS: BI-RADS 4a breast masses with a diameter less than 2 cm (n  = 143) were confirmed by pathology; 103 and 40 were classified as benign and malignant, respectively. The sensitivity, specificity, PPV, and NPV of CEUS for the diagnosis were 90%, 86%, 72%, and 95%, respectively. The area under the receiver operating characteristic (ROC) curve of CEUS for the diagnosis of benign and malignant tumors after CEUS was 0.904. CONCLUSION: CEUS can help to improve the diagnostic accuracy of BI-RADS 4a masses with a diameter less than 2 cm. Show more

Keywords: Contrast-enhanced ultrasound, BI-RADS-US 4a, breast, ultrasound

DOI: 10.3233/CH-221460

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Sun, Hongshuang | Ren, Yunyun

Article Type: Research Article

Abstract: AIM: The aim of this study was to investigate the role of cerebroplacental ratio (CPR) in the final prenatal care for neonatal respiratory diseases and to analyze the risk of relevant factors associated with neonatal respiratory disorders. METHODS: A prospective cohort study of 795 singleton pregnancies was conducted. The pulsatility indices (PI) of the umbilical artery (UA) and the middle cerebral artery (MCA) were measured, and the MCA to UA ratio (CPR) was determined. The severity of the case is determined by whether or not the newborn has respiratory problems. Compare the CPR correlation between the two groups …and examine the illness prediction factors through a binary logistic regression method. RESULTS: Of the 801 participants, 114 had neonatal respiratory disorders. The mean values of CPR between neonatal respiratory diseases group and control group were 1.78±0.6, 1.97±0.9, respectively (P  <  0.001). Maternal age, abortion history, cesarean section history, placental thickness, placental maturity, and amniotic fluid index (AFI) were determined to have no significant link between the two groups after comparison analysis (P >   0.05). It could be found that compared with the control group, CPR MoM indicators of neonatal respiratory distress syndrome, neonatal pneumonia and wet lung disease all show significant decreases. In binary logistic regression analysis, among the variables included in the model, CPR (OR:2.90, P  = 0.015), fetal heart monitoring (OR:5.26, P  <  0.001), delivery mode (OR:2.86, P  <  0.001) and gestational age of delivery (OR:0.92, P  <  0.001) were statistically significant in both groups. CONCLUSION: The findings of this study showed that infant respiratory problems were substantially related to CPR value. The correlation indicates that CPR was a powerful reference marker for respiratory disorders. Show more

Keywords: Cerebroplacental doppler ratio, fetal brain sparing, fetal lung maturation, neonatal respiratory disorders

DOI: 10.3233/CH-211333

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Wenzel, C. | Brix, E. | Heidekrueger, P. | Lonic, D. | Lamby, P. | Klein, S.M. | Anker, A. | Taeger, C. | Prantl, L. | Kehrer, A.

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVES: In complex hand traumas nerves and vessels are often destructed without the possibility for primary repair. For bridging defects of nerves, veins and arteries grafts are necessary. Commonly nerve and vein grafts from adjacent donor sites as the wrist, forearm or cubital region are harvested. METHODS: This study is a retrospective cohort study. Between 2017 and 2019, 10 patients with complex hand injuries were treated. There were 8 males and 2 females, with an average age of 39 years (range 8–63 years). In all cases grafts were used of the dorsum of the foot for …reconstructing of the severed digital nerves and arteries. All donor sites could be closed primarily. RESULTS: In 100% of cases nerves and veins of the dorsum of the foot showed a good size match as well as adequate length for a sufficient repair. The overall Hand Injury Severity Score (HISS) was determined with a median of 86 (range 57 to 286). In the area of the donor site no relevant complications were seen. CONCLUSIONS: In complex hand injuries the dorsum of the foot is a favorable donor site for nerve and vein graft harvest. Show more

DOI: 10.3233/CH-211135

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2022