Clinical Hemorheology and Microcirculation - Volume 83, issue 4

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. 83, no. 4, pp. 315-339, 2023

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. 83, no. 4, pp. 341-349, 2023

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. 83, no. 4, pp. 351-358, 2023

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. 83, no. 4, pp. 359-376, 2023

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. 83, no. 4, pp. 377-386, 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. 83, no. 4, pp. 387-395, 2023

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. 83, no. 4, pp. 397-408, 2023

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 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 area under the receiver operating characteristic curves (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, wash-in perfusion index (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

Keywords: Dynamic contrast enhanced ultrasound, thyroid nodule, time intensity curves, quantitative parameters, diagnosis

DOI: 10.3233/CH-221681

Citation: Clinical Hemorheology and Microcirculation, vol. 83, no. 4, pp. 409-420, 2023

Authors: Guntau, Moritz | Cucuruz, Beatrix | Brill, Richard | Bidakov, Oleksandr | Von der Heydt, Susanne | Deistung, Andreas | Wohlgemuth, Walter A.

Article Type: Research Article

Abstract: BACKGROUND/OBJECTIVE: Oral malformations of the tongue are exceedingly rare. The aim of this study was to evaluate the effectiveness of individualized treatment for patients with vascular malformations of the tongue. METHODS: This retrospective study is based on a consecutive local registry at a tertiary care Interdisciplinary Center for Vascular Anomalies. Patients with vascular malformations of the tongue were included. Indications for therapy of the vascular malformation were macroglossia with the impossibility to close the mouth, bleeding, recurrent infection and dysphagia. Size regression of the malformation (volume measurement) and symptom improvement were investigated. RESULTS: Out of 971 …consecutive patients with vascular malformations, 16 patients suffered from a vascular malformation of the tongue. Twelve patients had slow-flow malformations and 4 fast-flow malformations. Indications for interventions were bleeding (4/16, 25%), macroglossia (6/16, 37.5%), and recurrent infections (4/16, 25%). For two patients (2/16, 12.5%), there was no indication for intervention due to absence of symptoms. Four patients received sclerotherapy, 7 patients Bleomycin-electrosclerotherapy (BEST) and 3 patients embolization. Median follow-up was 16 months (IQR 7–35.5). In all patients, symptoms had decreased after two interventions at a median (IQR 1–3.75). Volume reduction of the malformation of the tongue was 13.3% (from median 27.9 cm3 to median 24.2 cm3 , p  = 0.0039), and even more pronounced when considering only patients with BEST (from 86 cm3 to 59.1 cm3 , p  = 0.001). CONCLUSION: Symptoms of vascular malformations of the tongue are improved after a median of two interventions with significantly increased volume reduction after Bleomycin-electrosclerotherapy. Show more

Keywords: Congenital vascular malformation of the tongue, slow-flow malformation, fast-flow malformation, Bleomycin-electrosclerotherapy, sclerotherapy, embolization

DOI: 10.3233/CH-221683

Citation: Clinical Hemorheology and Microcirculation, vol. 83, no. 4, pp. 421-429, 2023