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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-170298

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

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

Article Type: Research Article

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

Keywords: Ischemia, microcirculation, hemorheology

DOI: 10.3233/CH-170277

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

Authors: Gehmert, Sanga | Lehoczky, Gyözö | Loibl, Markus | Jung, Friedrich | Prantl, Lukas | Gehmert, Sebastian

Article Type: Research Article

Abstract: INTRODUCTION: Stromal-epithelial interactions are fundamental for normal organ development and there is a multitude of evidence that the different components of the microenvironment are also necessary for the maintenance and promotion of the “tumor organ”. Deregulated tumor associated extracellular matrix (tECM) is a hallmark of cancer, causing an alteration in the amount and composition of the different components (i.e. proteins, proteoglycans, glycoproteins and polysaccharids) of the ECM. As epithelial-stromal interactions are reciprocal, it is possible that tECM itself is able to initiate tumor development. We therefore established a mouse model to examine the influence of tECM of murine breast cancer …on developing breast tissue in mice. MATERIALS AND METHODS: Breast cancer was established in 5 BALB/c mice by subcutaneous injection of 1×106 4T1 cells in 100μl PBS into the left mammary fat pad. The mammary fat pad including the primary tumor was excised after two weeks, decellularised and labelled as tumor extracellular matrix (tECM). Tumor ECM of 4T1 tumors was implanted into the 4th inguinal mammary fat pad of BALB/c mice (n  = 5) aged 5 days. After 12 weeks the fourth mammary fat pad including the primary tumor was excised. Tissue was used for paraffin embedding and mouse breast cancer PCR array. Murine breast cancer tissue (BCT) and normal murine breast tissue (BT) served as control. RESULTS: Gene array analysis of 84 breast cancer-specific transcripts revealed that the mammary gland cells which were exposed to tumor ECM (tECM-BT) showed a similarly high overexpression for 22 genes as apparent for breast cancer tissue (BCT). The corresponding scatter plot showed a high agreement in the expression of the examined genes between the mammary gland cells which were exposed to tumor ECM and the breast cancer tissue. DISCUSSION: Our results clearly demonstrate that the tECM is able to shift the gene expression pattern of murine mammary epithelial cells towards that of carcinoma, indicating a role in breast cancer initiation. These data underlines that the acellular component of the tumor (ECM) can lead to a transformation of mammary gland tissue cells. These data show for the first time that the interaction of normal breast tissue cells with tumor ECM leads to an exchange of information and a consecutive overexpression of tumor-specific genes. Show more

Keywords: Breast cancer, extracellular matrix, microenvironment, epithelial-stromal interaction

DOI: 10.3233/CH-199234

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

Authors: Sievers, H. | Hiebl, B. | Hünigen, H. | Hirschberg, R.M.

Article Type: Research Article

Abstract: BACKGROUND: Blood supply is an important factor for the normal function of the equine hoof, but earlier studies present conflicting data on functional characteristics of its angioarchitecture. OBJECTIVE: Emphasis was laid on demonstration of the microvascularisation in the different hoof wall regions, aiming at assessment of specialised vascular structures, e.g. vascular sphincter mechanisms and arteriovenous anastomoses. METHODS: The angioarchitecture of the adult pododerma in the equine hoof wall was examined by scanning electron microscopy of micro-corrosion casts assisted by exemplary histological and immuno-histochemical characterisation of the pododermal vasculature. RESULTS: The microvasculature of the lamellae …and terminal papillae in all hoof wall regions was described in detail. Focal dilations and microvascular sphincters were a common feature. In contrast to former investigations, true arteriovenous anastomoses were detected at the base of the primary lamellae and the terminal papillae only, while thoroughfare channels proved a regular element within the microvasculature of the wall proper. Bicuspid venous valves were detected as regular feature. For the first time, the alpha-smooth muscle actin-reactivity of the microvascularisation in the hoof wall was systematically assessed, verifying its specialised vasomotor devices. CONCLUSIONS: The vasculature of the hoof wall displays specific angio-adaptations to high pressure and tensile load. Show more

Keywords: Blood vessels, microcirculation, wall segment, dermal lamellae, terminal papillae, sphincter vessels, pododermal angiogenesis

DOI: 10.3233/CH-199233

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-24, 2019

Authors: Wernly, Bernhard | Pernow, John | Kelm, Malte | Jung, Christian

Article Type: Research Article

Abstract: In the microcirculation, the exchange of nutrients, water, gas, hormones, and waste takes place, and it is divided into the three main sections arterioles, capillaries, and venules. Disturbances in the microcirculation can be measured using surrogate parameters or be visualized either indirectly or directly. Arginase is a manganese metalloenzyme hydrolyzing L-arginine to urea and L-ornithine. It is located in different cell types, including vascular cells, but also in circulating cells such as red blood cells. A variety of pro-inflammatory factors, as well as interleukins, stimulate increased arginase expression. An increase in arginase activity consequently leads to a consumption of …L-arginine needed for nitric oxide (NO) production by endothelial NO synthase. A vast body of evidence convincingly showed that increased arginase activity is associated with endothelial dysfunction in larger vessels of the vascular tree. Of note, arginase also influences the microcirculation. Arginase inhibition leads to an increase in the bioavailability of NO and reduces superoxide levels, resulting in improved endothelial function. Arginase inhibition might, therefore, be a potent treatment strategy in cardiovascular medicine. Recently, red blood cells emerged as an influential player in the development from increased arginase activity to endothelial dysfunction. As red blood cells directly interact with the microcirculation in gas exchange, this could constitute a potential link between arginase activity, endothelial dysfunction and microcirculatory disturbances. The aim of this review is to summarize recent findings revealing the role of arginase in regulating vascular function with particular emphasis on the microcirculation. Show more

Keywords: Microcirculation, arginase, atherosclerosis, intensive care, intravital microscopy, nitric oxide

DOI: 10.3233/CH-199237

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2019

Authors: Jokisch, F. | Buchner, A. | Schulz, G.B. | Grimm, T. | Weinhold, P. | Pfitzinger, P.L. | Chaloupka, M. | Stief, C.G. | Schlenker, B. | Clevert, D.-A.

Article Type: Research Article

Abstract: PURPOSE: The evaluation of the potential clinical benefit of four-dimensional ultrasound (4D-US) in the assessment of bladder cancer (BC). MATERIAL AND METHODS: 20 patients with indication for cystoscopy for suspicion of bladder cancer were prospectively included in this study. All patients underwent two-dimensional ultrasound (2D-US), contrast enhanced ultrasound (CEUS) and real-time four-dimensional ultrasound (4D-US). All acquisitions were compared to each other in regard to image quality. This assessment was done using a 6 point scale (1 = best). All patients underwent subsequently cystoscopy with resection of the tumor (TURB), due a histopathological analysis was possible. RESULTS: All examinations …were performed successfully and no patient had to be excluded from the study. Patients acceptance of 4D-US was consistently good. No adverse events occurred. Image quality of real time 4D-US (score: 1.27±0.46) was significantly superior (p  < 0.001) to both, conventional 2D-US (score: 2.33±0.62) and also to 2D-CEUS (score: 2.00±0.53). In terms of tumor detection no superiority was evident for 4D-US compared to 2D-US or in utilization of CEUS (sensitivity = 0.89; specificity = 1.00; positive predictive value = 1.00; negative predictive value = 0.50; AUC = 0.944; (95% CI: 07.43–0.998)). CONCLUSION: The assessment of bladder cancer using real time 4D-US is feasible and improves the image quality and therefore also the precise anatomical consistency of intravesical tumor masses. Show more

Keywords: Bladder cancer detection, real-time 4D ultrasound, four-dimensional ultrasound of the bladder, ultrasound of bladder cancer

DOI: 10.3233/CH-199231

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Puhr-Westerheide, D. | Kostbade, T. | Clevert, D.-A.

Article Type: Research Article

Abstract: BACKGROUND: Motorsport karting has developed into a professional international competition. Kart racing poses a unique set of physiologic challenges for athletes who compete in this sport. Until today no major study has evaluated the physical and cardiac challenge in professional kart racing. OBJECTIVE: The aim for this study was to measure and analyze heart rate and cardiac rhythm by a mobile, smartphone based ECG (s-patch) on professional kart-race-drivers during actual karting races through annual seasons to test the hypotheses that high g-force and stress could trigger cardiac arrhythmia. MATERIAL AND METHODS: ECG-data from kart-drivers were acquired …during local races, the ADAC Kart-Masters (KZ2), the German Kart Championship (DSKC) and the European Championship Senior CIK-FIA-Serie and analyzed in this observational study. In total, free practice, qualifying practice and 32 races were assessed during the kart season 2019. Data were interpreted by two independent experienced physicians. RESULTS: The average heart rate (HR) during a selected German Kart Championship (DSKC) race in Genk (Belgium) was 169 beats min-1. The longest R-R interval was 0.72 sec. The average HR during a selected European Championship CIK-FIA-race in Lonato (Italy) was 160 beats min-1. The longest R-R interval was 0.74 sec. The average HR during a selected ADAC Kart-Masters (KZ2) races in Wackersdorf (Germany) was 147 beats min-1. The longest R-R interval was 0.86 sec. In total 32 races could be recorded successful. No couplets or bigeminy cycles were detected. In one other kart racer a supraventricular extrasystole and a ventricular extrasystole was detected. Interestingly, kart-drivers were found to have sinustachycardia throughout the races most likely triggered by emotional and physiological stress during speeding. CONCLUSION: Professional kart racing drivers had sinustachycardia with heart rates up to 193 beats min-1 during races. This is most likely attributed to a considerably high emotional and physiological stress affecting the cardiovascular system. Episodes of tachycardia positively correlated with mean speed. In the warm-up lap the heart rate was significantly lower in comparison to the race, suggesting that faster driving speed would induce greater cardiovascular stress to professional drivers during actual races. The experimental results showed that the proposed S-patch system provided a good ECG signal quality with accurate measurements even during the kart race and could detect the ECG features of the race in real time. The cardiac interpretation software performs well and is a useful tool to assist clinicians. Show more

Keywords: S-patch, ECG, motorsport, karting

DOI: 10.3233/CH-199232

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

Authors: Lehoczky, Gyözö | Wolf, Francine | Mumme, Marcus | Gehmert, Sebastian | Miot, Sylvie | Haug, Martin | Jakob, Marcel | Martin, Ivan | Barbero, Andrea

Article Type: Research Article

Abstract: OBJECTIVE: Implantation of autologous chondrocytes for cartilage repair requires harvesting of undamaged cartilage, implying an additional joint arthroscopy surgery and further damage to the articular surface. As alternative possible cell sources, in this study we assessed the proliferation and chondrogenic capacity of debrided Knee Chondrocytes (dKC) and Nasal Chondrocytes (NC) collected from the same patients. METHODS: Matched NC and dKC pairs from 13 patients enrolled in two clinical studies (NCT01605201 and NCT026739059) were expanded in monolayer and then chondro-differentiated in 3D collagenous scaffolds in medium with or without Transforming Growth Factor beta 1 (TGFβ 1). Cell proliferation and …amount of cartilage matrix production by these two cell types were assessed. RESULTS: dKC exhibited an inferior proliferation rate than NC, and a lower capacity to chondro-differentiate. Resulting dKC-grafts contained lower amounts of cartilage specific matrix components glycosaminoglycans and type II collagen. The cartilage forming capacity of dKC did not significantly correlate with specific clinical parameters and was only partially improved by medium supplemention with TGFβ 1. CONCLUSIONS: dKC exhibit a reproducibly poor capacity to engineer cartilage grafts. Our in vitro data suggest that NC would be a better suitable cell source for the generation of autologous cartilage grafts. Show more

DOI: 10.3233/CH-199236

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

Authors: Tung, Wing Tai | Zou, Jie | Sun, Xianlei | Wang, Weiwei | Gould, Oliver E.C. | Kratz, Karl | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: Microfibers with a core-shell structure can be produced by co-axial electrospinning, allowing for the functionalization of the outer layer with bioactive molecules. In this study, a thermoplastic, degradable polyesteretherurethane, consisting of poly(p-dioxanone) (PPDO) and poly(ɛ -caprolactone) (PCL) segments with different PPDO to PCL weight ratios, were processed into fiber meshes by co-axial electrospinning with gelatin. The prepared PEEU fibers have a diameter of 1.3±0.5 μm and an elastic modulus of around 5.1±1.0 MPa as measured by tensile testing in a dry state at 37°C, while the PEEU/Gelatin core-shell fibers with a gelatin content of 12±6 wt% and a diameter of 1.5±0.5 …μm possess an elastic modulus of 15.0±1.1 MPa in a dry state at 37 °C but as low as 0.7±0.7 MPa when hydrated at 37 °C. Co-axial electrospinning allowed for the homogeneous distribution of the gelatin shell along the whole microfiber. Gelatin with conjugated FITC remained stable on the PEEU fibers after 7 days incubation in PBS at 37 °C. The gelatin coating on PEEU fibers lead to enhanced human adipose tissue derived mesenchymal stem cell (hADSC) attachment and a proliferation rate 81.7±34.1 % higher in cell number in PEEU50/Gelatin fibers after 7 days of cell culture when compared to PEEU fibers without coating. In this work, we demonstrate that water-soluble gelatin can be incorporated as the outer shell of a polymer fiber via molecular entanglement, with a sustained presence and role in enhancing stem cell attachment and proliferation. Show more

Keywords: PEEU, gelatin, electrospun fibers, mesenchymal stem cells, biomaterials

DOI: 10.3233/CH-199235

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2019

Authors: Mulder Pettersen, Erik | Avdal, Jørgen | Hisdal, Jonny | Torp, Hans | Seternes, Arne

Article Type: Research Article

Abstract: OBJECTIVE: In this proof-of-concept study we aim to validate a novel ultrasound Doppler monitoring device for evaluating microcirculation (earlybird) against LDF and pulsed Doppler. METHODS: In ten healthy subjects, we measured microcirculatory function at rest and during different autonomic tests (forced respiration, isometric exercise, Valsalva maneuver and cold pressor). Earlybird, LDF and pulsed Doppler were recorded simultaneously. We performed a ZNCC to determine correlation. RESULTS: The curves for earlybird and LDF or pulsed Doppler correlates visually well. Overall median ZNCC 0.87 (interquartile range 0.77 –0.91) between the LDF and earlybird measurements, and 0.90 (0.82 – 0.95) …for pulsed Doppler and earlybird. Median ZNCC for baseline and each provocation test for earlybird against LDF and pulsed Doppler were calculated; baseline: LDF 0.87 (0.73 – 0.97) pulsed Doppler 0.91 (0.81 – 0.94), forced respiration: LDF 0.87 (0.28 – 0.90) pulsed Doppler 0.90 (0.85 – 0.96), isometric exercise: LDF 0.82 (0.59 – 0.90) pulsed Doppler 0.87 (0.68 – 0.94), Valsalva maneuver: LDF 0.88 (0.82 – 0.91) pulsed Doppler 0.94 (0.92 – 0.97) and cold pressor: LDF 0.90 (0.85 – 0.95) pulsed Doppler 0.89 (0.65 – 0.94). CONCLUSION: Earlybird records vasoconstrictions in healthy subjects as well as LDF and pulsed Doppler. Show more

Keywords: Ultrasonography, Doppler, Laser-Doppler Flowmetry, peripheral arterial disease, inventions, microcirculation

DOI: 10.3233/CH-190707

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Negrão de Figueiredo, G. | Mueller-Peltzer, K. | Schwarze, V. | Marschner, C. | Zhang, L. | Rübenthaler, J. | Siepmann, T. | Illigens, B.W. | Clevert, D.A.

Article Type: Research Article

Abstract: BACKGROUND: Focal nodular hyperplasia (FNH) is a hyperplastic mass of vascular abnormality and the second most common benign liver lesion. It can be discovered incidentally or during a surveillance examination in patients at risk for hepatic malignancy, mostly by conventional ultrasound. CEUS has been used as an additional alternative method for the rapid diagnosis of FNH. However, none of the previous studies compared the diagnostic performance of CEUS to MRI retrospectively in a 10-year observation. OBJECTIVE: The aim of this long-term retrospective study is to assess the diagnostic performance of CEUS in the imaging of FNH and compare …the results to MRI. MATERIAL AND METHODS: A single experienced physician performed CEUS examinations in 244 patients between 2009 and 2019 with suspected focal nodular hyperplasia after conventional ultrasound. A second-generation blood pool agent (SonoVue® , Bracco, Milan, Italy) was administered. Additional dynamic MRI with contrast agent was performed in a subgroup of 95 patients. RESULTS: Out of 244 patients, FNH could be displayed in 221 patients on CEUS. A subgroup of 95 patients had CEUS examinations and CEMRI for diagnosis comparison. In comparison with CEMRI, CEUS presented a sensitivity of 97%, a specificity of 76%, a positive predictive value of 93% and a negative predictive value of 89%. CONCLUSION: CEUS is a safe and feasible approach that assess the diagnosis of focal nodular hyperplasia equally to MRI. The focal lesion enhancement can be depicted in real-time in the arterial, venous and late phase facilitating the prompt diagnosis. Show more

Keywords: CEUS, focal nodular hyperplasia, MRI, long-term study

DOI: 10.3233/CH-190710

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Caimi, Gregorio | Hopps, Eugenia | Montana, Maria | Carollo, Caterina | Calandrino, Vincenzo | Gallà, Eleonora | Canino, Baldassare | Lo Presti, Rosalia

Article Type: Research Article

Abstract: Protein carbonylation is a marker of oxidative protein damage, that is likely involved in the pathogenesis of several diseases. The aim of this study was to evaluate the protein carbonyl (PC) groups in different clinical conditions. It included different groups of subjects: 81 trained subjects; 23 subjects with mild essential hypertension; 31 middle-aged subjects with metabolic syndrome (MS); 106 subjects with MS not selected for age (subdivided into two subgroups, with and without diabetes mellitus); 91 obese adults subdivided in two subgroups (BMI 30–35 Kg/m2 and BMI > 35 kg/m2 ); 48 subjects with obstructive sleep apnea syndrome (OSAS) subdivided in …accordance with the apnea/hypopnea index (AHI); 27 subjects with chronic kidney disease (CKD) on conservative therapy; 31 subjects with CKD on haemodialysis treatment; and 50 subjects with juvenile myocardial infarction. PC groups were reduced in trained subjects in comparison with sedentary controls, while no variation was observed in mild essential hypertension. PC groups were increased in MS subjects and in adult obese subjects. In MS subjects the PC groups were not influenced by the presence of diabetes mellitus and in adult obese subjects were not influenced by the obesity degree. In OSAS subjects only those with AHI > 30 showed an increase of PC groups. PC groups increased in CKD subjects undergoing conservative treatment and haemodialysis therapy. In dialyzed subjects, after a standard dialysis session, there was a marked increase in PC groups. In juvenile myocardial infarction PC groups were higher than in controls; there was no difference between STEMI and NSTEMI and their concentration was unaffected by the number of cardiovascular risk factors or stenosed coronary vessels. Show more

Keywords: Oxidative stress, arterial hypertension, metabolic syndrome, juvenile myocardial infarction, chronic kidney failure

DOI: 10.3233/CH-190689

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2019

Authors: Liang, Ming | Ou, Bing | Wu, Jiayi | Xiao, Xiaoyun | Ruan, Jingliang | Tian, Jing | Xu, Xiaolin | Wang, Bin | Yang, Haiyun | Luo, Baoming

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the combined use of strain elastography (SE) and superb microvascular imaging (SMI) with grayscale ultrasound (US) according to the Breast Imaging Reporting and Data System (BI-RADS) classification for differentiating benign from malignant breast masses. METHODS: In total, 166 patients with 177 breast masses categorized as BI-RADS 3–5 were included in the study between April 2016 to September 2017. US, SMI and SE were performed to evaluate each mass. The following outcome measures were compared between US and the combinations of US, SMI, and SE: area under the receiver operating characteristic curve (AUC), sensitivity, specificity. …RESULTS: The addition of SMI and SE to US increased the AUC from 0.816 to 0.948 (P  < .001); and the specificity from 43.7% to 80.8% (P  < .001), without a significant decrease in the sensitivity. Meanwhile, 66.1% (37 of 56) of the benign masses that were indicated for unnecessary biopsy were correctly changed to follow-up. CONCLUSIONS: The addition SMI and SE to US could improve the diagnostic performance in differentiating benign from malignant breast masses compared to US alone. When US was combined with SMI and SE, the specificity were increased, thus significantly reducing unnecessary biopsies. Show more

Keywords: Breast cancer, superb microvascular imaging, strain elastography, ultrasonography

DOI: 10.3233/CH-190693

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

Authors: Gao, Yan | Zhu, Xiaolong | Huang, Lining | Teng, Jinliang | Li, Fulong

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to investigate the effects of dexmedetomidine on cerebral oxygen saturation [Sct(O2 )] and postoperative cognitive function in elderly patients undergoing minimally invasive coronary artery bypass graft surgery. METHODS: Sixty elderly patients who received minimally invasive coronary artery bypass graft surgery were randomly equally divided into dexmedetomidine group (group D) and control group (group N). The patients in group D were pumped with 1 μg/kg dexmedetomidine for 15 min before incision, followed by continuous pumping at 0.3–0.5 μg/(kg·h) till the end of the operation. The patients in group N received same dose of normal saline during …the operation. Sct(O2 ) was monitored at pre-induction (T0), post-induction (T1), 30 min (T2) after single-lung ventilation, and after surgery (T3). Mini-mental state examination (MMSE) was used to assess the cognitive function at 1 day before, 72 hour and 7 days after surgery. RESULTS: Sct(O2 ) level in group D was significantly higher than that in group N at T2 (P  < 0.05). Sct(O2 ) level was statistically lower at T2 than that at T0, T1 and T3 in the same group N (P  < 0.05). At 72 h and 7d after operation, the incidence of cognitive dysfunction in group D was markedly lower than that in group N (P  < 0.05), the MMSE score in group D was markedly higher than those in group N, but was significantly lower than that before surgery (P  < 0.05). CONCLUSION: Dexmedetomidine can alleviate the decrease of Sct(O2 ) during single-lung ventilation, improve postoperative cognitive function, and reduce the incidence of POCD in elderly patients with minimally invasive coronary artery bypass surgery. Show more

Keywords: Dexmedetomidine, minimally invasive coronary artery bypass surgery, elderly, cognitive dysfunction

DOI: 10.3233/CH-190590

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

Authors: Zhu, Jing | kang, Jing | Li, Xiaochen | Wang, Mengmei | Shang, Min | Luo, Yuchuan | Xiong, Mengqing | Hu, Ke

Article Type: Research Article

Abstract: BACKGROUND AND AIM: Both chronic intermittent hypoxia (CIH) and chronic continuous hypoxia (CCH) are risk factors for cardiovascular disease, which are associated with cardiac systolic function and associated with dysfunction of endothelia and coagulation-fibrinolysis system in the vasculature. However, the different effects of these two hypoxic models are not fully understood. In our study, we systemically compared the effects of CIH and CCH on cardiac function and related factor levels in serum using rat model. METHODS: Forty-five male Sprague-Dawley rats were randomly divided into the normoxia control (NC), CIH and CCH groups. The rat CIH and CCH models …were established, then the blood and tissue samples were collected to analyze the function of endothelium and the coagulation-fibrinolysis system. Also, the ultrasound cardiogram was performed to directly assess myocardial contractility. RESULTS: Both CIH and CCH significantly decreased the NO, eNOS, P-eNOS and AT-III levels in the rat serum but significantly increased the levels of ET-1, vWF, COX-2, NF-κ B, FIB, FVIII and PAI-1 in the rat serum (P  < 0.05). The expression of ET-1, VWF and ICAM-1 in CIH group were higher than CCH group (P  < 0.05), however, the expression of CD62p was increased in CCH group but not in CIH group. The expression of t-PA in CIH group were lower than CCH group (P  < 0.05), but there were no significant differences in CCH group and NC group (P  > 0.05). Using transmission electron microscope, we found that the mitochondrial ultrastructure of thoracic aorta endothelial cells in CIH and CCH group were damaged. Moreover, the myocardial contractility in CIH and CCH group were significantly decreased compared with NC group. CONCLUSION: Our results suggested that CIH and CCH could cause endothelial dysfunction, dysfunction of the coagulation-fibrinolysis system and decreasing of myocardial contractility. Compared with CCH, CIH has greater effect on vasoconstriction and adhesion of vascular endothelial cells, and stronger procoagulant effect. Show more

Keywords: Chronic intermittent hypoxia, chronic continuous hypoxia, vascular endothelial function, myocardial contractility

DOI: 10.3233/CH-190706

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

Authors: Sun, Xianlei | Tung, Wingtai | Zou, Jie | Wang, Weiwei | Kratz, Karl | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: BACKGROUND: The behavior of endothelial cell is remarkably influenced by the physical and biochemical signals from their surrounding microenvironments. OBJECTIVE: Here, the elasticity of fiber meshes was studied as a design parameter of substrates for endothelial cells in order to modulate angiogenesis. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured on electrospun fiber meshes made from polyetheresterurethane (PEEU), differing in their elasticity. Cell morphology, proliferation, migration and angiogenesis of endothelial cells on the degradable substrates meshes were characterized. RESULTS: The aspect ratio of HUVECs cultured on the fiber meshes from PEEU materials increased …with increasing stiffness of the materials. HUVECs cultured on fiber meshes with high stiffness (Young’s modulus E  = 4.5±0.8 MPa) presented a higher proliferation rate and significantly faster migration velocity, as well as higher tube formation capability than the cells cultured on fiber meshes with low stiffness (E  = 2.6±0.8 MPa). CONCLUSIONS: These results suggested that tuning the fiber meshes’ elasticity might be a potential strategy for modulating of the formation or regeneration of blood vessels. Show more

Keywords: Tensile E-modulus, HUVECs, electrospun fiber meshes, multiblock copolymers

DOI: 10.3233/CH-190696

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

Authors: Qiu, Yijie | Yang, Daohui | Zhang, Qi | Chen, Kailing | Dong, Yi | Wang, WenPing

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the feasibility of vector flow imaging technique (V Flow) in measurement of wall shear stress (WSS) of common carotid arteries (CCA) in healthy adults and to provide the normal WSS values assessed by V Flow. METHODS & MATERIALS: This prospective study was approved by the Ethics Committee of our University. Eighty healthy adult volunteers were included (mean age 43.3 y, 47 females, 33 males). The volunteers were classified into three groups according to their age: group I (age 20 - 39 y), group II (age 40 - 59 y) and group III (age 60 - …80 y). Mindray Resona 8 ultrasound machine and a linear array transducer (3–9 MHz) was used, equipped with the updated V Flow function. Common carotid arteries of both sides were evaluated in three segments (initial segment, middle segment and near bifurcation segment). The WSS values of CCA were measured by two independent radiologists. The intraclass correlation coefficient (ICC) of observer reliability in WSS measurement was calculated. Inter-observer reproducibility was also evaluated with the 95% Bland-Altman limits of agreement (LOA). RESULTS: V Flow measurements were performed successfully in 79 volunteers (98.8 %, 79/80). The mean value of WSS in right CCA was (0.66±0.24) Pa, in left CCA was (0.66±0.18) Pa (P  > 0.05). Mean WSS value had a moderately negative correlation with age group (P  < 0.05). The mean WSS value of group I(mean±SD, 0.75±0.25 Pa) is larger than group II (mean±SD, 0.62±0.13 Pa) and group III (mean±SD, 0.49±0.11 Pa) (P  < 0.05). The ICC of observer reliability of group I, II and III was 0.96 (95% confidence interval (95% CI) 0.92–0.98), 0.94 (95% CI 0.88–0.97), 0.93 (95% CI 0.76–0.98) respectively. The Bland-Altman plots showed that the 95% LOA were –0.17–0.12 (Pa) for group I, –0.09–0.13 (Pa) for group II and –0.08–0.10 (Pa) for group III. CONCLUSION: V Flow measurement is a simple, rapid and feasible imaging method for the WSS assessment of CCA in healthy volunteers, which will probably be an important tool for assessing CCA function. Show more

Keywords: Vector flow imaging (V Flow), wall shear stress (WSS), common carotid artery (CCA), feasibility, normal value

DOI: 10.3233/CH-190719

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

Authors: Kiss, Rudolf | Farkas, Nelli | Jancso, Gabor | Kovacs, Krisztina | Lenard, Laszlo

Article Type: Research Article

Abstract: INTRODUCTION: With the aging of the population, the screening of frail patients, especially before high-risk surgery, come to the fore. The background of the frail state is not totally clear, most likely inflammatory processes are involved in the development. METHODS: Our survey of patients over age of 65 who were on cardiac surgery were performed with Edmonton Frail Scale (EFS). Patients’ demographic, perioperative data, incidence of complications and correlations of inflammatory laboratory parameters were studied with the severity of the frail state. RESULTS: On the basis of EFS, 313 patients were divided into non-frail (NF,163,52%), pre-frail …(PF,89,28.5%) and frail (F,61,19.5%) groups. Number of complications in the three groups were different (NF:0.67/patient, PF:0.76/patient, F:1.08/patient). We showed significant difference between NF and F in both intensive care and hospital stay, but there was no statistical difference between the groups in hospital deaths (NF:5/163, PF:3/89, F:5/61). We also found a significant difference between NF and F patients in preoperative fibrinogen-, CRP- and white blood cell count levels. CONCLUSIONS: We first present the incidence of frailty in patients with heart surgery in a Central-European population. According to our results, inflammatory processes are likely to play a role in the development of the frail state. Show more

Keywords: Frailty, frail state, CRP, fibrinogen, cardiac surgery

DOI: 10.3233/CH-190681

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

Authors: Zhang, Shupin | Wan, Jing | Wu, Rong | Fang, Ya

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the efficacies of conventional ultrasound (US), US elasticity imaging (EI), and acoustic radiation force impulse (ARFI) elastography in breast malignancy diagnosis. METHODS: We included 315 women (mean age, 44 years; range, 18–81 years) with 336 pathologically proven breast lesions in this retrospective study. All lesions underwent conventional US, EI, and ARFI (including virtual touch tissue imaging [VTI], virtual touch tissue quantification [VTQ], and virtual touch tissue imaging and quantification [VTIQ]) elastography. Multivariate logistic regression analysis was performed to assess 12 independent variables for malignancy prediction. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve …analysis. RESULTS: Irregular lesion shape was the strongest independent predictor for breast malignancy, followed by poorly defined margins, taller than wide dimensions, posterior echo attention, VTIQ, and VTI boundaries (P  < 0.05). Area under the ROC curve (AUC) for VTIQ was higher than other significant independent variables. With the best cut-off value of 3.74 m/s, the AUC, sensitivity, and specificity were 0.93 (95% CI: 0.90, 0.96), 90.1%, and 91.1%, respectively. CONCLUSIONS: ARFI elastography is a promising method in breast malignancy prediction, with good diagnostic performance. For patients requiring surgery, the combination of various methods can provide better diagnostic results and may help to reduce unnecessary biopsy or surgery. Show more

DOI: 10.3233/CH-180527

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

Authors: Astapenko, David | Ticha, Alena | Tomasova, Adela | Hyspler, Radomir | Zadak, Zdenek | Lehmann, Christian | Cerny, Vladimir

Article Type: Research Article

Abstract: BACKGROUND: Endothelial glycocalyx (EG) is a carbohydrate-rich gel-like mesh covering the apical surface of endothelial cells. It has been linked to the microvascular pathophysiology and tissue metabolism. However, little is known about its condition in young healthy adults. OBJECTIVE: We aimed to describe the condition of EG in young healthy adults by in vivo EG imaging and measurement of syndecan-1, a plasma marker of EG integrity in order to obtain references values. METHODS: For in vivo EG studies we used Side-stream Dark Field imaging of the sublingual microcirculation. Recordings were analysed automatically by GlycoCheck …software providing the Perfused Boundary Region (PBR) as a marker of EG thickness. Levels of syndecan-1 were analysed in plasma samples by ELISA. RESULTS: 21 volunteers were included in the study. Median of the PBR value was 1.82 μm (interquartile range 1.69–2.01, 95% CI 1.79–1.97). Median concentration of syndecan-1 was 0.3 ng/ml (interquartile range 0.23–0.39, 95% CI 0.27–0.49). CONCLUSION: This study provides a comparison for cohorts of patients with a particular disease where the EG is presumably damaged. Our findings do not entirely comply with already published data in healthy individuals. Show more

Keywords: Endothelial glycocalyx, syndecan-1, healthy volunteers

DOI: 10.3233/CH-190581

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

Authors: Wu, Qiong | Li, Yi | Liu, Yilun | Shen, Jian | Wang, Yan | Yi, Xiaolei | Hu, Bing

Article Type: Research Article

Abstract: PURPOSE: The aim of this study was to evaluate the diagnostic value of conventional sonography and ultrasound elastography for thyroid nodules of each Bethesda category and to analyze their potential role in the corresponding management decision. METHODS: This retrospective study included 557 thyroid nodules diagnosed by conventional ultrasound (US) and real-time ultrasound elastography (RTE) before fine-needle aspiration (FNA) from 458 patients. The US, RTE, and cytological results were collected and analyzed according to different Bethesda categories. Differences in the distribution of sonographic features between groups were evaluated by the Chi-square test or Fisher exact test. The sensitivity, specificity, …positive predictive value, negative predictive value, and accuracy of conventional US and RTE for the diagnosis of malignant nodules in each category were then calculated and analyzed. RESULTS: The diagnostic accuracy of the comprehensive US diagnosis in all categories stayed at a relatively high level from 78.4% to 88.6%, and good specificities ranging from 77.3% to 100% were revealed in all Bethesda categories. As to RTE, the diagnostic accuracies in categories I–IV stayed at a relatively low level ranging from 44.6% to 65.6% except for better performance in categories V and VI (85.2%, 89.1%). Besides, the accuracies of comprehensive US (85.2%, 88.6%) and RTE (85.2%, 89.1%) is relatively low compared to the corresponding cytological diagnoses in categories V and VI. CONCLUSIONS: Conventional US is complementary to FNA for providing additional hints especially in categories I–IV for further clinical managements, while RTE failed to provide useful diagnostic information in general. Show more

Keywords: Thyroid nodules, fine-needle aspiration, conventional US, real-time ultrasound elastography, Bethesda category

DOI: 10.3233/CH-180533

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Shi, You-Zhen | Jin, Yan | Zheng, Li

Article Type: Research Article

Abstract: OBJECTIVES: To identify the associated factors for malignancy in partially cystic thyroid nodules (PCTNs) on ultrasound (US). MATERIALS AND METHODS: This is a retrospective study. 338 PCTNs confirmed by surgery was included in this study. The US features of the nodules were reviewed and their significance in differential diagnosis was analyzed. RESULTS: In the 338 PCTNs, 50 were malignant and 288 were benign. Univariate analyses revealed that a taller-than-wide shape and spiculated or microlobulated margin were significantly associated with malignancy while the spongy form, an ovoid to round shape and smooth margin were significantly associated with …benign nature. In terms of the internal solid portion of the nodule, eccentric configuration, non-smooth margin, hypoechogenicity, and microcalcification were more frequently demonstrated in malignant nodules than in benign ones. In the multivariate logistic regression analysis, a taller than wide shape (OR: 13.357; 95% CIs: 3.457–28.797) was revealed to be the strongest independent predictor for malignancy, followed by microcalcification (OR: 11.578; 95% CIs: 3.142–29.563), spiculated or microlobulated margin (OR: 6.331; 95% CIs: 1.425–9.457), eccentric configuration (OR: 5.456; 95% CIs: 1.358–8.774), non-smooth rim of the internal solid portion (OR: 4.897; 95% CIs: 0.754–7.021), and hypoechogenicity of the internal solid portion (OR: 4.651; 95% CIs: 0.712–8.245). CONCLUSIONS: Understanding the ultrasound characteristics of malignant PCTNs is important to make a precise diagnosis of thyroid nodules. Show more

Keywords: Partially cystic thyroid nodules, conventional ultrasound

DOI: 10.3233/CH-190582

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

Authors: Auer, Timo Alexander | Fischer, Thomas | Garcia, Stephan Rodrigo Marticorena | Penzkofer, Tobias | Jung, Ernst-Michael | Hamm, Bernd | Lerchbaumer, Markus Herbert

Article Type: Research Article

Abstract: BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique in order to evaluate focal liver lesions. CEUS is easy and fast to perform, overcomes the limitations of B-mode US. OBJECTIVE: To evaluate the diagnostic potential of contrast-enhanced ultrasound (CEUS) in focal liver lesions (FLL) with unclear findings on computed tomography (CT) or magnetic resonance imaging (MRI). METHODS: In this single-center retrospective study, 146 patients with at least one FLL underwent additional CEUS of the liver to clarify inconclusive cross-sectional imaging findings. Ultrasonography was performed using B-mode imaging and CEUS after injection of sulphur …hexafluoride microbubbles (second-generation contrast agent) within two months after ceMRI or ceCT and interpreted by an experienced radiologist (EFSUMB level 3). Histopathological reports, long-term follow-up or clinical course served as reference standard. RESULTS: Thirty-eight of the 146 patients had malignant and 108 benign FLL. Overall, CEUS had 92% sensitivity (95% -CI, 79–97) and 98% specificity (95% -CI, 93–99) with an AUC of 0.95 in correctly characterizing the lesion as malignant or benign. Sensitivity increased to 98% (95% -CI, 96–100) for benign lesions and decreased to 92% (95% -CI, 78–98) for malignant lesions. CEUS showed the highest diagnostical accuracy in lesion <1 cm with an AUC of 1.000, while the lowest accuracy was achieved in lesions >2 cm with an AUC of 0.924 due to a decreasing specificity of 86% (95% -CI, 87–100). CONCLUSION: CEUS correctly distinguished malignant from benign FLL in cases with inconclusive cross-sectional imaging findings and achieved high levels of diagnostic accuracy. CEUS has added diagnostic value especially in small lesions ≤1 cm while specificity remains limited in larger lesions. Show more

Keywords: CEUS, focal liver lesions, sonography, contrast-enhanced ultrasound, liver ultrasound

DOI: 10.3233/CH-190718

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

Authors: Bakker, Nathalie | Schoorl, Marianne | Stoutjesdijk, Eline | Houdijk, Alexander P.J.

Article Type: Research Article

Abstract: BACKGROUND: An adequate erythrocyte function is vital for tissue oxygenation and wound healing. The erythrocyte membrane phospholipid composition plays an important role in erythrocyte function and administration of omega-3 fatty acids may provide a means to improve it. OBJECTIVE: To investigate peri-operative erythrocyte function and effects of omega-3 fatty acids METHODS: Forty-four patients undergoing elective laparoscopic colon resection for non-metastasized cancer were randomized between intravenous omega-3 poly-unsaturated fatty acids (n-3 PUFAs) or placebo (saline). Peri-operative blood samples were analyzed with a Lorrca MaxSIS Ektacytometer and erythrocyte membrane phospholipids were determined with gas chromatography. RESULTS: …Patient and operation characteristics were equal between groups. There was a significant increase in erythrocyte membrane eicosapentaenoic acid (EPA) but not docosahexaenoic acid (DHA) in the n-PUFA group. There were no significant differences in erythrocyte deformability but the aggregation index (AI) was significantly lower and the aggregation half time (T½) was significantly higher in the n-3 PUFA group. CONCLUSION: This study confirms rapid changes in erythrocyte membrane phospholipid composition after administration of intravenous n-3 PUFAs. Erythrocyte deformability parameters were not affected but erythrocyte aggregability was decreased in the n-3 PUFA group. Further investigation is necessary to gain more insights in the effects of n-3 PUFA and the postoperative inflammatory response on erythrocyte function. Show more

Keywords: Erythrocytes, deformability, aggregability, colon cancer surgery, omega-3 fatty acids

DOI: 10.3233/CH-190687

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

Authors: Ding, Xiaohu | Lu, Lin | Yang, Jing | Chen, Yijiao | Ma, Jin

Article Type: Research Article

Abstract: PURPOSE: To explore the peripapillary capillary density distribution and its correlation with nerve fibre layer in superficial and deep retinal layers of healthy Chinese. METHODS: Images of superficial and deep retinal capillary networks were obtained by optical coherence tomography angiography (OCTA) using a CIRRUS TM HD-OCT Model 5000 system and analyzed by Image-Pro Plus (Medical Cybernetics, Version 6.0). Peripapillary capillary density was defined as the mean optical density of the annular region between two concentric circles of 3.085 mm and 3.835 mm diameter. Parafoveal capillary density was defined as the mean optical density between the foveal avascular zone (FAZ) boarder …and a 2.5 mm diameter circle. Retinal nerve fibre layer (RNFL) thickness was also measured and the correlation with capillary density determined. RESULTS: Mean peripapillary capillary density was 4.16±1.06 in the superficial and 2.92±0.80 in the deep layer. Corresponding mean parafoveal densities were 2.65±0.55 and 2.51±0.55. Capillary densities were higher in the superficial layer of all quadrants for both peripapillary and parafoveal regions (P  <  0.001). A significant correlation between peripapillary capillary density and RNFL thickness was found in the superficial layer (r  = 0.305, P  <  0.05). A negative correlation between age and capillary density was found in both peripapillary and parafoveal regions (P  <  0.001). CONCLUSIONS: Peripapillary capillary density in the superficial layer highly correlated with RNFL thickness. Regional and age-related differences in peripapillary and parafoveal capillary density should be considered when diagnosing and monitoring individuals with diseases affecting retinal capillary density. Show more

Keywords: Capillary density, Optical coherence tomography angiography (OCTA) angiogram, Retinal nerve fibre layer

DOI: 10.3233/CH-180453

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

Authors: Koch, Christoph | Taeger, Christian | Geis, Sebastian | Lonic, Daniel | Heidekrueger, Paul | Dolderer, Juergen | Bitzinger, Diane | Hirche, Christoph | Prantl, Lukas | Kehrer, Andreas

Article Type: Research Article

Abstract: BACKGROUND: Purpura fulminans (PF) is a distinct form of rare meningococcal septicaemia mostly in childhood which is characterized by high lethality, extensive necroses and mutilations of extremities. Other ethiologies are idiopathic forms or purpura neonatorum, which is marked by deficiency of Protein-C. PF is caused by micro-embolism of the vascular system, followed by quickly spreading necroses of skin and different organs. Modern concepts of intensive care treatment of the acute phase of this disease and early surgical intervention lead to a rising number of surviving patients requiring limb salvage. Aim of this study is to evaluate a possible lower morbidity …and the grade of lower loss of function because of early surgical intervention. PATIENTS AND METHODS: Between the years 1998 and 2017 cases of PF at two large centers for critical wound care, the department of plastic-, hand- and reconstructive surgery of the university hospital of Regensburg and the department of plastic-, hand- and reconstructive surgery of the BG-clinic Ludwigshafen patients were included into our study. We retrospectively examined patients with PF who were stabilized by intensive care medicine and received surgical interventions. After survival of the acute phase (10 days), patients received plastic surgical reconstructions. RESULTS: A total number of eight patients could be included into our study. All patients survived the initial phase (10 days). All patients required plastic-surgical interventions to address extensive skin and soft tissue defects. Flap operations were judged necessary in five cases. Hereby four defects could be reconstructed by free tissue transfer, one with a local flap. Flap survival was 100 percent. One flap required revision of the arterial anastomosis of the flap arteria. Another flap got partial necrosis. One patient died due to multiorgan failure. Early debridements with consequent fasciotomies and secondary plastic-surgical reconstruction achieved good functional results. Limb salvage was accomplished in three patients. One patient died due to fulminant progress of the disease. CONCLUSION: Management of PF requires a multidisciplinary approach and close communication between the different subspecialties. Early debridements with consequent fasciotomies showed good results in salvaging subfascial muscle tissue in the extremities with satisfying functional results. Early surgical intervention is an important factor for improved limb salvage and survival. Show more

Keywords: Purpura fulminans, symptoms, surgical management, intensive care management, Idiopathic Thrombocytopenic Purpura, Disseminated Intravascular Coagulation, Acquired Protein C Deficiency, Sepsis, Neisseria meningitidis, Menigococcal sepsis, streptococcus pyogenes, herpes simplex virus

DOI: 10.3233/CH-190588

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Yi, Dong | Benhua, Xu | Qiong, Cao | Qi, Zhang | Yijie, Qiu | Daohui, Yang | Lingyun, Yu | Wen-Ping, Wang

Article Type: Research Article

Abstract: AIM: To investigate the value of contrast enhanced ultrasound with high resolution linear transducers (HF-CEUS) for differential diagnosis of focal fundal gallbladder (GB) wall thickening. METHODS: A total of 32 patients with incidentally detected focal fundal GB wall thickening were included. After conventional B mode ultrasound (BMUS) examinations, HF-CEUS were performed with a 7.5–12 MHz 9L4 linear transducer (S2000 HELX OXANA unit, Siemens). Two radiologists independently reviewed the HF-CEUS enhancement patterns to determine the differential features between malignancy and benignity with a five-point confidence scale. The diagnostic accuracy of BMUS and HF-CEUS for GB wall thickening was compared. The …final gold standard was surgery with histological examination. RESULTS: Final diagnoses included GB adenocarcinoma (n  = 16), adenomyomatosis (n  = 12), Xanthogranulomatous (n  = 2) and cholecystitis (n  = 2). HF-CEUS features associated with GB adenocarcinoma including arterial phase inhomogeneous hyperenhancement, venous phase hypoenhancement and disruption of GB wall layer structure (P  <  0.05). Two small (5 mm) liver metastasis were confirmed by HF-CEUS during the late phase liver sweep as hypoenhanced lesions. Nonenhanced Rokitansky-Aschoff sinuses were clearly observed in 83.3% focal adenomyomatosis. Overall sensitivity, specificity and accuracy for differentiation between malignant and benign focal fundal GB wall thickening of HF-CEUS and BMUS were 84.3% vs 53.1%, 90.6% vs 59.3% and 87.5% vs 56.2% (P  <  0.005). CONCLUSIONS: CEUS performed with high frequency linear transducers could be a useful alternative in the differential diagnosis of focal fundal GB wall thickening on conventional ultrasound. Show more

Keywords: Gallbladder, contrast enhanced ultrasound (CEUS), linear transducer, differential diagnosis, focal wall thickening

DOI: 10.3233/CH-190697

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

Authors: Wang, S. | Li, B. | Yin, T. | Hong, J. | Gu, J. | Wei, L.

Article Type: Research Article

Abstract: BACKGROUND: The aneurysmal subarachnoid hemorrhage (aSAH) is an acute severe hemorrhagic stroke with high morbidity and mortality with poor prognosis. OBJECTIVE: This study aims to analyze the changes of cerebral venous circulation in patients with aneurysmal subarachnoid hemorrhage by digital subtraction angiography (DSA). MATERIALS AND METHODS: Totally, 57 patients with aSAH, 48 patients with unruptured aneurysms, and 45 patients without aneurysms (control group) were enrolled. The microvascular cerebral circulation time (mCCT), venous cerebral circulation time (vCCT), cerebral arterioles and cortical veins were analyzed by DSA. RESULTS: There were changes of cerebral microvessels and cortical …veins in patients with aSAH. The mCCT (6.15±1.37 s) and vCCT (2.79±0.34 s) of aSAH patients significantly increased compared with control patients (3.74±0.50 s; 2.64±0.32 s) (P  <  0.05). However, the mCCT increased more compared with vCCT in aSAH patients (P  <  0.001), while the vCCT increased more compared with mCCT in severe aSAH cases (P  <  0.01). There was no significant difference in mCCT and vCCT between patients with unruptured aneurysms and controls (P  = 0.131; P  = 0.621). CONCLUSIONS: The mCCT increases in acute aSAH patients within 72 hours and vCCT increases in severe aSAH cases. Show more

Keywords: Aneurysmal subarachnoid hemorrhage, cerebral vein, digital subtraction angiography, microvascular cerebral circulation time, venous cerebral circulation time

DOI: 10.3233/CH-190573

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Chayer, Boris | Allard, Louise | Qin, Zhao | Garcia-Duitama, Julian | Roger, Laurence | Destrempes, François | Cailhier, Jean-François | Denault, André | Cloutier, Guy

Article Type: Research Article

Abstract: BACKGROUND: An enhanced inflammatory response is a trigger to the production of blood macromolecules involved in abnormally high levels of erythrocyte aggregation. OBJECTIVE: This study aimed at demonstrating for the first time the clinical feasibility of a non-invasive ultrasound-based erythrocyte aggregation quantitative measurement method for potential application in critical care medicine. METHODS: Erythrocyte aggregation was evaluated using modeling of the backscatter coefficient with the Structure Factor Size and Attenuation Estimator (SFSAE). SFSAE spectral parameters W (packing factor) and D (mean aggregate diameter) were measured within the antebrachial vein of the forearm and tibial vein …of the leg in 50 healthy participants at natural flow and reduced flow controlled by a pressurized bracelet. Blood samples were also collected to measure erythrocyte aggregation ex vivo with an erythroaggregometer (parameter S 10 ). RESULTS: W and D in vivo measurements were positively correlated with the ex vivo S 10 index for both measurement sites and shear rates (correlations between 0.35–0.81, p  <  0.05). Measurement at low shear rate was found to increase the sensitivity and reliability of this non-invasive measurement method. CONCLUSIONS: We behold that the SFSAE method presents systemic measures of the erythrocyte aggregation level, since results on upper and lower limbs were highly correlated. Show more

Keywords: Erythrocyte aggregation, quantitative ultrasound, shear rate control, human, clinical measurements

DOI: 10.3233/CH-180541

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2019

Authors: Li, Guanhua | Zhang, Yu | Tang, Wei | Zheng, Junmeng

Article Type: Research Article

Abstract: BACKGROUND: Polyamidoamine (PAMAM) dendrimers have been investigated for decades and currently applied in various areas throughout nanomedicine, including gene therapy, drug delivery, anti-bacteria and imaging. It is therefore necessary to assess cytotoxicity of PAMAM dendrimers systematically. Because blood components are usually the initial step of contact with any therapeutic agent, comprehensive hemocompatibility study is needed. MATERIAL S AND METHODS: The triblock dendrimer: polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD), was successfully synthesized. Various in vitro assays to characterize hemocompatibility of both PAMAM (Generation 4.0) and PAMAM-PEG-cRGD were performed, including hemolytic assay, platelet activation examination, platelet counting, assessment of coagulating pathways …and evaluation of complement system activation. RESULTS: The hemolytic ratio of PAMAM-PEG-cRGD maintained below 5%. Surface engineering of PEG and cRGD to PAMAM attenuated hemolysis and RBC aggregation as compared with unmodified PAMAM. PAMAM (Generation 4.0) reduced platelet counting in a dose-dependent manner, and the platelet number dropped dramatically at a relatively low incubating dose (1 μ M). Such surface modifications also alleviated platelet activation and platelet reduction mediated by PAMAM polycationicity. Finally, high concentration (10μ M) of PAMAM interfered the coagulation system, prolonging prothrombin time significantly. CONCLUSION: Surface modification of PEG and cRGD to PAMAM (Generation 4.0) improves hemocompatibility. Introduction of PEG and cRGD significantly mitigates hemolytic and RBC aggregation effects as compared with unmodified PAMAM. Similarly, these modifications alleviate platelet activation and platelet reduction mediated by PAMAM polycationicity. Show more

Keywords: Polyamidoamine (PAMAM), dendrimer, nanoparticle, hemocompatibility, surface modification

DOI: 10.3233/CH-190641

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

Authors: Raberin, Antoine | Nader, Elie | Ayerbe, Jorge Lopez | Mucci, Patrick | Connes, Philippe | Durand, Fabienne

Article Type: Research Article

Abstract: Blood rheology and hemodynamic parameters have never been explored together during acclimatization to altitude. This study aimed to investigate changes in blood rheology parameters and pulmonary hemodynamics during the first days of real moderate altitude exposure. Seventeen athletes were tested at sea-level, 20 hours after their arrival at 2,400 meters of altitude (H1) and five days later (H2). Blood was sampled to analyze red blood cell (RBC) aggregation, blood viscosity and hematocrit. Pulmonary arterial pressure (PAP), pulmonary capillary pressure (Pcap) and pulmonary vascular resistance (PVR) were assessed by echocardiography. We observed a rise in hematocrit, blood viscosity, RBC …aggregation, PAP, Pcap and PVR between sea-level and H1. In H2, RBC aggregation, hematocrit, PAP, Pcap and PVR remained different compared to SL and no difference was observed between H1 and H2. Blood viscosity decreased in H2 and returned to sea-level values. Our results suggest that hemoconcentration occurring within the first hours of altitude exposure increased blood viscosity, which contributed to the changes in pulmonary hemodynamic. When blood viscosity decreased in H2, no change occurred in pulmonary hemodynamic parameters suggesting that hypoxic pulmonary vasoconstriction was still present. The elevated RBC aggregation observed after in H2 could participate in the increase of Pcap. Show more

Keywords: Moderate altitude, pulmonary arterial pressure, pulmonary vascular resistance, blood viscosity, red blood cell aggregation

DOI: 10.3233/CH-190671

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

Authors: Xie, Juan

Article Type: Research Article

Abstract: PURPOSE: To evaluate the diagnostic value of quantitative shear wave elastography (SWE) for the differential diagnosis of solid pancreatic tumors. MATERIALS AND METHODS: A total of 66 solid pancreatic masses were enrolled in this study and all the lesions underwent quantitative SWE. The stiffness of the masses was expressed in shear wave velocity (SWV, m/s). The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic performance of quantitative SWE. The optimal cutoff value for SWV in the differentiation of benign from malignant masses was determined. RESULTS: The final diagnoses were 26 benign and 40 …malignant masses. The SWVs were statistically higher for pancreatic malignant masses compared with those for benign masses (3.30±1.22 m/s versus 1.31±0.64 m/s; P  <  0.001). The area under the curve (AUC, 0.93) was obtained. When the best cut-off point was 1.77 m/s, the accuracy, sensitivity, and specificity were 92.4%, 90.0%, and 96.2%, respectively. CONCLUSIONS: Quantitative SWE is a novel technique that can be considered as a quantitative and objective diagnostic tool for prediction of pancreas malignancy. Show more

Keywords: Elasticity imaging techniques, pancreatic neoplasms, ultrasonography

DOI: 10.3233/CH-190665

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

Authors: Wang, Yali | Wu, Feng | Hu, Feng | Wu, Yunjiang | Zhou, Jun | Xu, Yan | Shao, Xiangrong | Hu, Tao

Article Type: Research Article

Abstract: Drag-reducing polymers (DRPs) was previously demonstrated to increase blood flow, tissue perfusion, and reduce vascular resistance. The purpose of this study was to investigate the effect of DRPs on pulmonary vascular remodeling and right ventricular dysfunction in a rat model of chronic hypoxia-induced pulmonary hypertension (HPH). A total of forty male Wistar rats were randomly and equally assigned into four experimental groups (Group I: normoxia + saline, Group II: normoxia + PEO, Group III: hypoxia + saline, Group IV: hypoxia + PEO) and maintained in normoxia (21% O2 ) or hypobaric hypoxia (10% O2 ). After four weeks, comparisons were …made of the following aspects: the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP), right ventricular hypertrophy, wall thickness of pulmonary trunk and arteries, internal diameter of pulmonary arteries, cardiomyocyte cross-sectional area (CM CSA), and ultrastructure of right ventricular. Treatment with PEO in Group IV attenuated the increases in RVSP and mPAP (40.5±7.2 and 34.7±7.0 mmHg, respectively, both P  <  0.05), compared with Group III. Distal vascular remodeling was visible as a significant increase in medial wall thickness (64.2±12.3% vs. 43.95±7.0%, P  <  0.01) and a remarkable decrease in internal diameter of small pulmonary arteries (35.2±9.7μ m vs. 50.4±14.7μ m, P  <  0.01) in Group III, to a greater extent than that detected in Group IV. Nevertheless, no significant histopathological differences in medial wall thickness was observed in pulmonary trunk between Group III and Group IV (P  >  0.05), denoting that PEO chiefly attenuated the remodeling of small pulmonary arteries rather than main arteries in hypoxic environment. Infusion of DRPs (intravenous injection twice weekly) also attenuated the index of right ventricular hypertrophy, protected against the increase of cardiomyocyte cross-sectional area, and provided protection for cardiac ultrastructure. DRP treatment with intravenous injection elicited a protective effect against pulmonary vascular remodeling and right ventricular dysfunction in the rat model of HPH. DRPs may offer a new potential approach for the treatment of HPH, which may have theoretical significance and application value to society. Show more

Keywords: Drag-reducing polymers, vascular remodeling, right ventricular, chronic hypoxia, pulmonary hypertension

DOI: 10.3233/CH-190668

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Sirufo, Maria Maddalena | Ginaldi, Lia | de Martinis, Massimo

Article Type: Research Article

Abstract: Volleyball players are exposed to the possibility of several well recognized injuries, among which microvascular abnormalities are the less described and studied, although they could diminish their ability and performance. Capillaroscopy is a simple, non-invasive method to diagnose vascular abnormalities in athletes suffering for the consequences of repeated application of pressure by local trauma on the fingertips. The detected capillaroscopic picture will be the base for the follow-up and will indicate the possible need for further investigations aimed at excluding other occulted conditions. At our knowledge, this is the first report describing and documenting the related microvascular abnormalities in a …volleyball player. This case emphasizes the fact that volleyball players among other athletes, whose hands are exposed to repeated fingertips trauma may suffer from microcirculation damage, for which reason they should be able to access an effective health surveillance program able to detect the first signs and offer the most appropriate clinical support. Show more

Keywords: Volleyball, athletes, sport, capillaroscopy, hand, injury, microcirculation, translational medicine

DOI: 10.3233/CH-190667

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-5, 2019

Authors: Vosseler, Markus | El Shazly, Ahmed | Parker, John D | Münzel, Thomas | Gori, Tommaso

Article Type: Research Article

Abstract: BACKGROUND: Evidence of a circadian rhythm in endothelium-dependent vasomotor function, with a nadir in Flow-Mediated Dilation (FMD) in the early morning hours, has been previously reported. These changes have been proposed to be one of the mechanisms explaining the circadian pattern in the incidence of cardiovascular events. We set out to investigate the circadian rhythm of FMD, low-flow mediated dilation (L-FMC) and sympathetic vascular tone. METHODS AND RESULTS: 10 young healthy male volunteers (mean age, 28.9±3.7 years) underwent measurements of radial artery endothelium-dependent FMD and L-FMC at 8AM, 2PM and 8PM on the same day. Sympathetic vascular tone …was assessed with laser Doppler and Fourier transform analysis. Compared with 2PM and 8PM, FMD decreased markedly in the early morning (2.9±3.4%; 6.2±2.9%; 6.0±4.0%; P  = 0.007). In contrast, L-FMC was maximal at 8AM, decreased significantly at 2PM, and returned to higher values at 8PM (–5.1±1.3%; –2.7±2.0%; –4.6±2.2%; P  = 0.030), such that the composite endpoint of endothelial function (sum of FMD+L-FMC) was not significantly different among timepoints. Vascular sympathetic tone was maximal early in the morning and lowest in the evening (P  = 0.014) without a correlation with the changes in FMD or L-FMC. CONCLUSIONS: Endothelial responsiveness (FMD) and basal tone (L-FMC) appear to follow different circadian rhythms, with an impaired responsiveness in the early morning and a nadir in baseline tone in the early afternoon. Show more

Keywords: Endothelial function, circadian rhythm, vascular physiology

DOI: 10.3233/CH-190587

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

Authors: Ederer, I.A. | Goertz, O. | Bosselmann, T. | Sogorski, A. | Zahn, P.K. | Lehnhardt, M. | Daigeler, A. | Kolbenschlag, J.

Article Type: Research Article

Abstract: BACKGROUND: Mechanism of remote ischemic conditioning (RIC) remain not fully understood yet. Thus, we performed a clinical trial to assess the neuronal influence on its signal induction. METHODS: RIC was conducted on 45 patients who were randomized into 3 groups. Group A and B underwent brachial plexus anesthesia while RIC was performed on the blocked (A) and non-blocked side (B), respectively. In group C, RIC was conducted before regional anesthesia, thus serving as control group. All measurements were taken contralateral to RIC. The relative increase of microcirculatory parameters compared to baseline was evaluated and compared between the groups. …RESULTS: Superficial blood flow (sBF) significantly increased in group A and C but values were higher among group C. Compared to group A, group C showed a significant increase of sBF during the initial 5 minutes of reperfusion (1.75; CI 1.139 – 2.361 vs . 0.97, CI 0.864 – 1.076, p  <  0.05). Deep blood flow, tissue oxygen saturation and relative hemoglobin content were marginally influenced by RIC irrespectively of the presence of regional anesthesia. CONCLUSION: Despite regional anesthesia a significant RIC stimulus can be induced although its microcirculatory response is attenuated compared to control. Hence, RIC induction does not merely depend on neuronal signaling. Show more

Keywords: Remote ischemic conditioning, neuronal signaling, plexus anesthesia, microsurgery, reperfusion

DOI: 10.3233/CH-190626

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Astapenko, David | Turek, Zdenek | Dostal, Pavel | Hyspler, Radomir | Ticha, Alena | Kaska, Milan | Zadak, Zdenek | Skulec, Roman | Lehmann, Christian | Cerny, Vladimir

Article Type: Research Article

Abstract: BACKGROUND: Endothelial glycocalyx (EG) is a carbohydrate-rich vascular lining of the apical surface of endothelial cells. It has been proved to have an essential role in vascular homeostasis. Lipid emulsions as part of parenteral nutrition (PN) are widely used in patients in the setting of critical care and perioperative medicine. Due to their structure, lipids may potentially interact with EG. The aim of the study was to evaluate the effect of lipid emulsion on EG. OBJECTIVE: To assess the influence of lipid emulsion on EG integrity in ICU patients using a videomicroscopic and biochemical methods. METHODS: …Patients in surgical ICU after major abdominal surgery or cardio surgery and in general ICU were assessed for eligibility for this pilot observational study in University Hospital. The study was performed during the first day of adding lipids as a part of their PN. The patients were given the SMOFlipid 20% for 6 hours in prescribed dose of approx. 1 g/kg of body weight. EG integrity was measured indirectly by automated sublingual videomicroscopy calculating a parameter PBR which describes the amount of lateral deviation of red blood cells from the central column and by levels of syndecan-1 and syndecan-4 in plasma as EG degradational products. Measurements were performed before lipid administration (T0) and 30 minutes after (T6) the infusion of lipid emulsion was completed. The statistical analysis was performed at the level of significance p  < 0.05, data are expressed as mean ± standard deviation (SD) and for PBR as median and interquartile range (IQR). RESULTS: Fifteen patients were studied, from them 9 included in final analysis. PBR (expressed in μ m) increased after the lipid infusion with no statistical significance (T0 = 2.10; 1.97–2.33 vs. 2.28; 2.11–2.45, p  = 0.13). At T6 both syndecans showed statistically significant decrease in their particular levels. Syndecan–1 at T0 = 2580±1013 ng/l, resp. at T6 = 2365±1077 ng/l, p  = 0.02; syndecan–4 at T0 = 134±29 ng/l, resp. at T6 = 123±43 ng/l, p  = 0.04. CONCLUSION: In our study, we showed that six hours long SMOFlipid 20% infusion had no detrimental effect on the EG integrity as assessed by PBR value and by syndecan-1 and syndecan-4 plasmatic levels. Observed decrease of syndecans shortly after lipid infusion allows us to hypothesize even possibly protecting effect of lipids on EG. Show more

Keywords: Endothelial glycocalyx, lipid emulsion, syndecan-1, syndecan-4, perfused boundary region, critically ill

DOI: 10.3233/CH-190564

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

Authors: Dong, Yi | Liu, Lingxiao | Cao, Qiong | Zhang, Qi | Qiu, Yijie | Yang, Daohui | Yu, Lingyun | Wang, Wen-Ping

Article Type: Research Article

Abstract: BACKGROUND AND AIM: To evaluate the benefits of contrast-enhanced ultrasound (CEUS) with high frequency transducers in characterization of focal gallbladder lesions (FGL). MATERIAL AND METHODS: From January 2017 to April 2019, 59 FGL detected by B mode ultrasound (BMUS) were examined, first with the low frequency convex transducer (1–5 MHz) and afterwards with high frequency transducer (7.5–12 MHz). High frequency dynamic CEUS were applied after bolus injection of 4.8 ml Sulphur hexafluoride microbubbles (SonoVue® , Milan). The BMUS and CEUS imaging features were recorded and compared. All lesions were confirmed by surgical resection and histopathologic results. RESULTS: The final …diagnoses of 59 FGL included gallbladder adenocarcinoma (n  = 15), gallbladder polyps (n  = 11), gallbladder adenomas (n  = 18), focal adenomyomatosis (n  = 9), and gallbladder Ascariasis debris (n  = 6). The mean diameter of FGL was 24.5±11.4 mm, and mean depth to the abdominal wall was 21.2±7.3 mm. While applying CEUS with high frequency transducer, specific diagnostic features, including arterial phase irregular intralesional vascularity (10/15, 66.7%), late phase hypoenhancement (12/15, 80%), destruction of gallbladder wall (8/15, 53.3%), infiltration to the adjacent liver (6/15, 40.0%) were significantly higher in malignant FGL. The overall sensitivity, specificity and diagnostic accuracy for the correct characterization of malignant FGL were significantly improved by CEUS with high frequency transducer (sensitivity 93.3%, specificity 88.5%, accuracy 100%). CONCLUSION: With its superior contrast resolution, CEUS performed with high frequency transducers is helpful to achieve better visualization of gallbladder fundus and make differential diagnosis of gallbladder lesions, which might greatly improve diagnostic confidence between malignant and benign FGL. Show more

Keywords: Contrast enhanced ultrasound (CEUS), focal gallbladder lesion, high frequency, diagnosis, differentiation

DOI: 10.3233/CH-190639

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Lin, Lirong | Zhang, Yaxuan | Zeng, Qingxin | Lin, Ligong | Geng, Xiaoli | Wang, Shaobin

Article Type: Research Article

Abstract: OBJECTIVE: To study the atherosclerosis (AS), inflammatory factor level, cognitive disorder and vascular endothelial functions in patients with different grades of leukoaraiosis (LA), and to explore the correlations of different grades of LA with cognitive disorder. METHODS: A total of 180 patients with cerebral infarction admitted and treated in the Department of Neurology of our hospital were selected, and they were graded according to the Tarvonen-shcolder standard, with 45 patients in each group. The atherosclerotic plaques of the patients were detected via a color Doppler ultrasound system and magnetic resonance imaging (MRI). Their inflammatory factor levels were determined …using enzyme-linked immunosorbent assay (ELISA). The cognitive function was scored based on the mini-mental state examination (MMSE), and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), endothelin (ET) and nitric oxide (NO) were measured to evaluate vascular endothelial functions. RESULTS: According to the comparisons among four groups of the patients, the incidence rate of AS was gradually increased among patients with different grades of LA (p  < 0.05). With the aggravation of LA, the levels of inflammatory factors in patients were obviously increased (p  < 0.05). LA patients had evidently lowered MMSE scores and levels of SOD and NO, but notably raised inflammatory factors C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) and vascular endothelial function indices MDA and ET (p  < 0.05). CONCLUSION: The occurrence of LA is implicated with the increasing levels of inflammatory factors in the patients, aggregation of cognitive dysfunction and impairment vascular endothelial functions. Show more

Keywords: Leukoaraiosis, atherosclerosis, inflammatory factors, cognitive function, vascular endothelial functions

DOI: 10.3233/CH-190597

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

Authors: Ugurel, Elif | Connes, Philippe | Yavas, Gokce | Eglenen, Buse | Turkay, Mine | Aksu, Ali Cenk | Renoux, Celine | Joly, Philippe | Gauthier, Alexandra | Hot, Arnaud | Bertrand, Yves | Cannas, Giovanna | Yalcin, Ozlem

Article Type: Research Article

Abstract: BACKGROUND: Erythrocyte deformability is impaired in sickle cell disease (SCD). The regulation of cytoskeletal protein organization plays a key role in erythrocyte deformability. The activation of adenylyl cyclase (AC)/cAMP/Protein kinase A (PKA) signaling pathway was associated with increased deformability in healthy erythrocytes, however the role of this pathway in SCD is unknown. OBJECTIVE: We evaluated mechanical responses of sickle red blood cells under physiological levels of shear stress and the possible link between their deformability and AC/cAMP/PKA signaling pathway. METHODS: The shearing of sickle red blood cells at physiological level (5 Pa) and the measurement of …deformability were performed by a laser assisted optical rotational cell analyzer (LORRCA). RESULTS: Red blood cell deformability increased of 2.5–6.5% by blocking the activity of phosphodiesterase with Pentoxifylline (10μ M) (p  < 0.05). The inhibition of AC with SQ22536 (100μ M) produced more significant rise in deformability (+4.8–12%, p  < 0.01). No significant change was observed by the inhibition of PKA with H89 (10μ M). CONCLUSION: Pentoxifylline and SQ22536 increased the deformability of sickle red blood cells under fluid shear stress. Modulation of the AC/cAMP/PKA pathway could have the potential to be an effective therapeutic approach for SCD through shear-induced improvements of RBC deformability. Show more

Keywords: Protein kinase a, adenylyl cyclase, phosphodiesterase, red blood cell deformability, sickle cell disease

DOI: 10.3233/CH-190563

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

Authors: Chen, Baoding | Zhang, Zheng | Wang, Keke | Shang, Mengyuan | Zhao, Shuangshuang | Ding, Wenbo | Du, Rui | Yu, Zhuan | Xu, Ximing

Article Type: Research Article

Abstract: OBJECTIVE: To analyze the association of BRAFV600E mutation with ultrasonographic (US) features and clinicopathologic characteristics in Chinese patients with papillary thyroid microcarcinoma (PTMC). METHODS AND MATERIALS: We retrospectively reviewed 116 consecutive Chinese patients with PTMC diagnosed by postoperative pathology. The incidence of the BRAFV600E mutation was calculated. The US features and clinicopathologic characteristics were compared between BRAF-positive and BRAF-negative patients. RESULTS: The BRAFV600E mutation was detected in 60.3% of patients (70 of 116). Multifocality (OR: 3.681, P  = 0.031), non-parallel orientation (OR: 3.181, P  = 0.041) and lymph node metastasis (OR: 4.615, P  = 0.009) were …significantly associated with BRAFV600E mutation. Other US and clinicopathologic characteristics were not significantly related to the presence of BRAF mutation. CONCLUSION: Multifocality, non-parallel orientation and cervical lymph node metastasis are risk factors for BRAFV600E mutation in PTMC. These factors potentially guide treatment planning or prognosis evaluation. Show more

Keywords: BRAFV600E mutation, ultrasonographic features, clinicopathologic characteristics, papillary thyroid microcarcinoma

DOI: 10.3233/CH-190568

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

Authors: Caimi, G. | Raso, S. | Napolitano, M. | Hopps, E. | Presti, R. Lo | Siragusa, S.

Article Type: Research Article

Abstract: Although the inherited quantitative and qualitative disorders of fibrinogen are rare, in the course of time patients may develop complications including episodes of arterial and venous thrombosis. It can be useful to complete the laboratory assessment of these clinical conditions with the evaluation of the haemorheological profile. The data obtained from this study showed that congenital afibrinogenemia was characterized by a primary plasma hypoviscosity, whereas congenital dysfibrinogenemia by a primary plasma hyperviscosity. Both these haemorheological alterations may concur, with different mechanisms, to the pathogenesis of thrombotic vascular complications.

DOI: 10.3233/CH-180542

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

Authors: Rothe, Rebecca | Schulze, Sabine | Neuber, Christin | Hauser, Sandra | Rammelt, Stefan | Pietzsch, Jens

Article Type: Research Article

Abstract:  The treatment of critical-size bone defects following complicated fractures, infections or tumor resections is a major challenge. The same applies to fractures in patients with impaired bone healing due to systemic inflammatory and metabolic diseases. Despite considerable progress in development and establishment of new surgical techniques, design of bone graft substitutes and imaging techniques, these scenarios still represent unresolved clinical problems. However, development of new active substances gives cause for hope. This work discusses therapeutic approaches that influence angiogenesis or hypoxic situations in healing bone and surrounding tissue. In particular, literature on sphingosine-1-phosphate receptor modulators and nitric oxide (NO• ) …donors, including bi-functional (hybrid) compounds like NO• -releasing cyclooxygenase-2 inhibitors, was critically reviewed with regard to their local and systemic mode of action. Show more

Keywords: Critical-size bone defects, neovascularization, nitric oxide donors, signaling, small molecules, sphingosine-1-phosphate receptor

DOI: 10.3233/CH-199103

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-30, 2019

Authors: Rothe, Rebecca | Schulze, Sabine | Neuber, Christin | Hauser, Sandra | Rammelt, Stefan | Pietzsch, Jens

Article Type: Research Article

Abstract:  Critical-size bone defects after compound fractures, infection, or tumor resection are challenging to treat. The same is true for fractures in patients with impaired bone healing due to metabolic diseases and cancer. Despite considerable progress over the last decade in surgical techniques, material design, and dedicated imaging approaches, these scenarios represent unsolved clinical problems. The high socioeconomic burden of such conditions justifies increasing interest in novel osteoinductive drugs for adjuvant therapeutic approaches. There is an increasing body of experimental and clinical literature on potentially promising effects of growth factors, anti-resorptive, and anabolic agents. The true clinical efficacy of these, however, …is discussed controversially. Therefore, we aimed to critically examine the hypothesis that targeted adjuvant therapies have the potential to enhance bone regeneration in critical-size bone defects and under systemic conditions that impair bone healing. This first approach to the topic deals with small molecule drugs and compounds that influence the immune response and inflammatory processes. In particular, literature reporting on selective cyclooxygenase-2 inhibitors has been reviewed with respect to their local and systemic mode of action and to stimulate further research on bone healing under critical conditions. Show more

Keywords: Biomaterials, critical-size bone defects, cyclooxygenase-2, innate immunity, prostanoids, signaling, small molecules

DOI: 10.3233/CH-199102

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-28, 2019

Authors: Rothe, Rebecca | Schulze, Sabine | Neuber, Christin | Hauser, Sandra | Rammelt, Stefan | Pietzsch, Jens

Article Type: Research Article

Abstract: In this third in a series of reviews on adjuvant drug-assisted bone healing, further possibilities of influencing the healing process are discussed. Local and systemic modulation of bone metabolism is considered during use of a number of drugs with completely different indications, which are characterized by a pleiotropic spectrum of action. These include drugs used to treat lipid disorders (HMG-CoA reductase inhibitors), hypertension (ACE inhibitors), osteoporosis (bisphosphonates), cancer (proteasome inhibitors) and others. Possibilities of their application in the support of bone healing arediscussed.

Keywords: Bisphosphonates, bone metabolism, critical-size bone defects, small molecules, statins, strontium, Wnt signaling

DOI: 10.3233/CH-199104

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-53, 2019

Authors: Jung, Friedrich | Pietzsch, Jens

Article Type: Editorial

DOI: 10.3233/CH-199101

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 2019

Authors: Geyer, Beatrice | Poch, Franz G. M. | Gemeinhardt, Ole | Neizert, Christina A. | Niehues, Stefan M. | Vahldiek, Janis L. | Klopfleisch, Robert | Lehmann, Kai S.

Article Type: Research Article

Abstract: BACKGROUND: Animal liver is established as an ex vivo model for studies on hepatic microwave ablation (MWA). Macroscopically visible color changes in the ablation zone are used to assess cell destruction and confirm successful ablation ex vivo . OBJECTIVE: Macroscopy and histology of MWA zones regarding cell viability in ex vivo porcine livers were compared in this study. METHODS: Six MWA were performed in porcine livers post mortem. A 14-G antenna and microwave generator (928 MHz; 9.0 kJ) were used. MWA were cut at the maximum cross section in vertical alignment to the antenna. NADH-diaphorase staining …determined cell vitality. Macroscopic and microscopic ablation zones were statistically analyzed. RESULTS: Histology showed two distinct ablation zones: central white zone (WZH) with no cell viability and peripheral red zone (RZH) with partial cell viability. However, the macroscopically visible WZM was significantly smaller than the microscopic WZH with an area difference of 43.1% (p  < 0.05) and a radius difference of 21.2% (1.6 mm; p  < 0.05). Macroscopy and histology showed a very high correlation for the complete lesion area (WZH/M+RZH/M; r  = 0.9; p  = 0.001). CONCLUSIONS: The avital central zone is significantly larger as the macroscopically visible WZ which is commonly used to assess successful ablation in MWA ex vivo studies. Irreversible cell destruction can be underestimated in macroscopic evaluation. Show more

Keywords: Liver, ex vivo, animal model, microwave ablation (MWA), viability staining, NADH-diaphorase

DOI: 10.3233/CH-190583

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

Authors: Gilicze, Orsolya | Simon, Diana | Farkas, Nelli | Lantos, Mate | Jancso, Gabor | Berki, Timea | Lenard, Laszlo

Article Type: Research Article

Abstract: BACKGROUND: Composition of pericardial fluid (PF) may reveal immunological processes influencing oxidative stress and microcirculation of different tissues of the heart and may play a role in the course of myocardial infarction, atherosclerosis, and aortic stenosis. PATIENTS AND METHODS: We investigated lymphocyte populations, cardiovascular markers and immunoglobulin composition in PF and blood samples of patients undergoing CABG operation and compared them to those who had aortic valve surgery. RESULTS: The amount of CD8 + T, NK, memoT and activated T-cytotoxic cells were elevated in PF compared to blood, but naiveT and activated T-helper cell ratio were lower in …PF. Amount of activated T-helper cells and regulatory T-lymphocytes were elevated in CABG participants in both PF and blood. INKT cells represented the only regulatory lymphocyte population reaching significantly higher concentration in PF than in blood. IL-6 and MCP1 level were elevated in PF compared to blood and MCP1 plasma level was markedly elevated in CABG group. CONCLUSIONS: Our study describes a comprehensive immunological analysis of PF in humans for the first time. We showed that the investigated lymphocyte populations and cardiovascular markers in PF have significantly different distribution compared to blood, and lymphocyte populations show different compartmentization in coronary disease and aortic stenosis. Show more

Keywords: Lymphocyte populations, cardiovascular markers, immunoglobulin, pericardial fluid, ischemic heart disease, calcific aortic stenosis

DOI: 10.3233/CH-190594

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Ezer, Erzsebet | Schrick, Diana | Tőkés-Füzesi, Margit | Szapary, Laszlo | Bogar, Lajos | Molnar, Tihamer

Article Type: Research Article

Abstract: BACKGROUND: Elevated mean platelet volume (MPV) and immature platelet fraction (IPF) are predictive for vascular risk. Both can be associated with residual platelet reactivity. We aimed to explore associations among platelet characteristics and responder status in stroke patients on clopidogrel. METHODS: Blood samples from 46 patients and 15 healthy subjects were analyzed for platelet count, MPV, IPF, large cell ratio (LCR) and high-fluorsecent immature platelet fraction (H-IPF). As a novelty, not only whole blood, but upper and lower half blood samples after 1-hour gravity sedimentation were analyzed. Platelet aggregometry was used for the whole blood and separated samples …to explore area under the curve (AUC) in patients and controls. RESULTS: The AUC of the whole blood showed significant differences compared to the upper and lower samples separated after 1-hour sedimentation in patients and controls (p  < 0.001 and p  = 0.005 respectively). Remarkably, AUC measured in the upper samples in 59% of patients on clopidogrel were exceeding the therapeutic range suggesting that ascending platelets exert aggregation in the presence of ADP. This observation was associated with increased MPV and LCR in the upper samples (both p  = 0.04). Patients on clopidogrel were characterized as responders and non-responders and the percentage of H-IPF was significantly higher among non-responders compared to controls in the upper samples (p  = 0.04). CONCLUSIONS: The modified platelet function test may help to stratify patients with high residual platelet reactivity. Show more

Keywords: Immature platelet, clopidogrel, aggregometry, ischemic stroke

DOI: 10.3233/CH-190580

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

Authors: Islam, Sufia | Ahmed, Najneen | Rivu, Sanzana Fareen | Khalil, Marjana | Tanjia, Nafisa | Lehmann, Christian

Article Type: Research Article

Abstract: BACKGROUND: Microvascular dysfunction is a main contributor to morbidity and mortality worldwide. Sophisticated technical tools (e.g. miniaturizedhardware, automated software), along with skilled personnelare the prerequisite for quantitative observations of the microvasculature. OBJECTIVE: This review aimed to get anoverviewabout on-goingmicrocirculatory research in developing countries, particularly of the South-East Asia region for the last five years and to project the challenges faced in microcirculation research in developing countries. METHODS: Original research articles originating from 194 countries were searched in PubMed database on the field of microcirculation research for the last five years. RESULTS: Our findings showed …that around 1800 articles have been published from developing countries compared to more than 5000 from developed countries on different aspects of microcirculation. The overall publication per million populations for developing countries was found to be 0.36 where for developed countries it was 3.62. CONCLUSIONS: Initiation and executionof sophisticated research in microcirculation is a demand of the time. Such research, initially, may seem unmanageable in developing countries with limited resourcesand infrastructuresettings. Collaborativescientificprojectsmay aid in establishingnetworks for microvascular research in developing countries. Show more

Keywords: Microcirculation, infrastructure, developed countries, developing countries

DOI: 10.3233/CH-190611

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

Authors: Lerchbaumer, Markus Herbert | Auer, Timo Alexander | Marticorena, Garcia Stephan | Stephan, Carsten | Hamm, Bernd | Jung, Ernst-Michael | Fischer, Thomas

Article Type: Research Article

Abstract: BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique in order to clarify testicular findings. CEUS is easy and fast to perform, overcomes the limitations of B-mode US. OBJECTIVE: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the assessment of unclear testicular pathologies. METHODS: CEUS examinations of 45 patients with unclear testicular pathologies between 2012 and 2018 were analyzed retrospectively. Examinations were performed using B-mode, colour Doppler (CCDS) and CEUS after injection of contrast agent (SonoVue® , Bracco) and interpreted by an experienced radiologist (EFSUMB level 3). Reference standard was defined …as histopathological report and clinical course. RESULTS: Overall 19 patients presented with a neoplastic lesion, whereas 14 were malignant. Matched to the histopathological report and clinical follow up, CEUS represented a sensitivity of 93% (95% -CI, 69–99), a specificity of 94% (95% -CI, 80–98), a positive predictive value (PPV) of 87% (95% -CI, 62–96) and a negative predictive value (NPV) of 97% (95% -CI, 83–99). CONCLUSION: CEUS is an accurate additional tool to differentiate between testicular alterations when B-mode US and CCDS are uncertain. CEUS may provide additional information and detect early enhancement in small tumor lesions when CCDS comes to its limit. Show more

Keywords: Contrast-enhanced ultrasound, CEUS, testis, testicular pathology

DOI: 10.3233/CH-190579

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

Authors: Rohm, Ilonka | Grün, Katja | Müller, Linda Marleen | Bäz, Laura | Förster, Martin | Schrepper, Andrea | Kretzschmar, Daniel | Pistulli, Rudin | Yilmaz, Atilla | Bauer, Reinhard | Jung, Christian | Berndt, Alexander | Schulze, P. Christian | Franz, Marcus

Article Type: Research Article

Abstract: Growing evidence suggests that inflammation is crucially involved in the pathogenesis of pulmonary hypertension (PH) and consecutive right heart failure. The present study analyzed the inflammatory response in lung and right ventricle in a rat model of PH and evaluated the effects of the dual endothelin receptor antagonist (ERA) Macitentan. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in Sprague-Dawley rats (PH, n  = 10) and compared to healthy controls (CON, n  = 10) as well as monocrotalin-induced, macitentan-treated rats (THER, n  = 10). Detection of Dendritic cells (DCs), regulatory T cells (Tregs) and others as well as RT-PCR based inflammatory gene …expression analysis were performed. Circulating DCs and Tregs were quantified by flow cytometry in the rat model and in PH patients (n  = 70) compared to controls (n  = 52). Inflammatory cells were increased in lung and right ventricular tissue, whereas DCs and Tregs were decreased in blood. Expression of 17 genes in the lung and 20 genes in the right ventricle were relevantly (>2.0 fold) regulated in the PH group. These effects were, at least in part, attenuated in response to Macitentan treatment. In humans as well as rats, immune cells showed significant correlations to clinical, echocardiographic, and haemodynamic parameters. PH is accompanied by a distinct inflammatory response in lung and right but not left ventricular tissue attenuated by Macitentan. Correlations of circulating DCs as well as tissue resident immune cells with parameters reflecting right ventricular function raise the idea of both, promising biomarkers and novel treatment strategies. Show more

Keywords: pulmonary hypertension, right heart failure, inflammation, biomarker, dual endothelin receptor antagonist

DOI: 10.3233/CH-180529

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-26, 2019

Authors: Chen, Chao-Tsung | Hsu, Chung-Hua | Liu, Jyh-Rou | Wu, Hung-Bo | Chou, Yi-Sheng | Hsiu, Hsin

Article Type: Research Article

Abstract: This study tested the hypothesis that measuring and analyzing skin-surface blood flow dynamics can be used to noninvasively discriminate the different microcirculatory and physiological function states of breast-cancer patients with chemotherapy between receiving and not receiving Kuan-Sin-Yin (KSY) treatment. The 17 included patients were assigned randomly to 2 comparison groups: Group K (n  = 10) received KSY treatment, while Group NK (n  = 7) did not receive KSY treatment. Beat-to-beat, spectral, and approximate-entropy (ApEn) analyses were applied to the 20-minute laser-Doppler sequences. The self-reported quality of life and cancer-related symptoms of patients were also investigated. In posttests, Group NK had a significantly …larger ApEn ratio than that in Group K, significantly smaller values of laser-Doppler-flowmetry variability indices, and a slightly higher relative energy contribution of the neural-related frequency band compared to those in the pretests. Almost all cancer-related symptoms showed improvements in Group K compared to in Group NK. The present findings indicated that the present analysis can be used to detect the significantly different responses in the laser-Doppler indices between taking and not taking KSY. The KSY effect was also noted to be accompanied with improvement of EORTC QLQ-C30 scores. These could lead to a rapid, inexpensive, and objective technique for enhancing clinical applications in quality-of-life monitoring of breast cancer therapy. Show more

Keywords: Breast cancer, blood flow, laser Doppler, approximate entropy, spectral analysis

DOI: 10.3233/CH-190569

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

Authors: Liu, Shui-Qing | Xie, Xiao | Liu, Yan-Ping | Ma, Yi-Bo | Zhang, Ling | Ge, Hong-Wei | Ding, Jiu-Le | Xing, Xiao-Xiao

Article Type: Research Article

Abstract:  Uterine arteriovenous malformation (AVM) is an extremely rare condition characterized by abnormal connections between veins and arteries. The atypical clinical manifestations and relatively low morbidity of AVM are conducive to missed diagnosis. The present study describes a case of a 47-year-old female patient with congenital uterine AVM followed by iatrogenic AVM. The diagnosis was established by contrast-enhanced ultrasound combined with contrast-enhanced CT (CECT). Because the symptom of vaginal bleeding was severe, trophoblastic disease or neoplasia could be preferred. The manifestations on various imaging examinations were carefully assessed, and the relevant literature was also reviewed.

Keywords: Uterine arteriovenous malformation, contrast-enhanced ultrasound, contrast-enhanced computed tomography, conventional ultrasound

DOI: 10.3233/CH-180489

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2019

Authors: Veres, T.Gy. | Petrovics, L. | Sárvári, K. | Vereczkei, A. | Jancsó, G. | Farkas, K. Borbásné | Takács, I.

Article Type: Research Article

Abstract: INTRODUCTION: Pneumoperitoneum, widely used in laparoscopic surgery increases the intraabdominal pressure, leading to hypoperfusion of the abdominal organs, and promoting the buildup of reactive oxygen species(ROS) and inflammatory cytokines which in turn impairs the body postoperatively. Aim of our investigation was to evaluate the potential protective effects of short ischemic episodes on ischemic damages. METHODS: 70 Wistar rats were used, divided into 7 groups: 1st group sham, 2nd group pneumoperitoneum with 5 mmHg, 3rd group preconditioning with 5 mmHg, 4th group: postconditioning with 5 mmHg, 5th group pneumoperitoneum with 10 mmHg, 6th group: preconditioning with 10 mmHg, 7th group postconditioning with 10 mmHg. Pneumoperitoneum …was created by Veres needle. Oxidative stress parameters: malondialdehyde (MDA) concentration, reduced glutathione (GSH), sulfhydril (SH-), myeloperoxidase (MPO) levels and superoxide-dismutase (SOD) activity were measured. We measured TNF-α and IL-6 concentrations. We monitored the activation of anti- and proapoptotic common signaling pathways (bax, bcl-2, p53) during the early phase of reperfusion. Histology was made from kidney samples. RESULTS: GSH concentrations were significantly reduced, MDA concentrations were significantly higher in each group compared to the Sham. SOD enzyme: a pressure of 10 mmHg elicited significantly greater damage than 5 mmHg. There was a significantly higher SOD activity in group 10 mmHg IPC compared to 10 mmHg. We found that the expression of bax was considerably higher in the none conditioned groups. Noticeably higher expression of anti-apoptotic bcl-2 level was measured in 10 mmHg IPC and 10 mmHg IPoC groups. In case of p53 expression: significant decrease could be seen in groups 10 mmHg IPC and 10 mmHg IPoC compared to the 10 mmHg group. CONCLUSION: Based on our results, the elevated intraabdominal pressure due to pneumoperitoneum induces oxidative stress, which is dependent on the applied pressure. Mostly precondiotioning – but also postconditioning – reduces surgical stress following laparoscopic procedures. In order to explore its mechanism it requires further investigations. Show more

Keywords: Laparoscopy, preconditioning, postconditioning, oxidative stress

DOI: 10.3233/CH-190572

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

Authors: Biran, Roni | Hadayer, Noa | Ramot, Yuval | Zlotogorski, Abraham | Yedgar, Saul | Barshtein, Gregory

Article Type: Research Article

Abstract: BACKGROUND: Alternations in erythrocyte deformability (ED), namley, the ability of erythrocytes to change shape under flow in the microcirculation, can contribute to cardiovascular diseases. Psoriasis, a systemic inflammatory skin disorder, is associated with an increased cardiovascular risk. The effect of psoriasis and psoriasis treatment on ED was only scarcely evaluated. OBJECTIVE: To evaluate ED changes in psoriasis patients following narrow band-ultraviolet B (NB-UVB) treatment. METHODS: Erythrocyte deformability was determined using a computerized cell flow properties analyzer in 9 patients with psoriasis before and after a course of Goeckerman regimen. ED was quantified using two parameters: average …elongation ratio (AER) in the cell population, and the fraction of low deformable cells (% LDFC). RESULTS: All 9 patients showed decreased ED (i.e. impaired deformability) following NB-UVB treatment. There was a significant (p  = 0.003) decrease in AER after treatment (AER±SD; 1.58±0.06) compared to the starting values (1.69±0.1). Additionally, there was a significant (p  = 0.002) increase in the fraction of low deformable cells (% LDFC±SD; 60.00±9.05) compared to their fraction before treatment (34.86±11.44). CONCLUSIONS: The decreased ED observed following phototherapy could have clinical influences on psoriasis patients, and may partially explain why phototherapy does not decrease the cardiovascular risk in psoriasis compared to other treatments. Show more

Keywords: Psoriasis, phototherapy, erythrocytes, deformability, comorbidities, cardiovascular disease

DOI: 10.3233/CH-180424

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

Authors: Han, Hong | Ji, Zhengbiao | Ding, Hong | Zhang, Weibin | Zhang, Ronghui | Wang, Wenping

Article Type: Research Article

Abstract: PURPOSE: To evaluate micro-flow imaging (MFI) in depicting the vascular architecture of hepatocellular carcinoma (HCC) and other focal liver lesions. MATERIALS AND METHODS: A total of 81 hepatic lesions were enrolled in this study. Each patient underwent CDFI, MFI, and CEUS examinations. The blood flow was first graded into three types (grade 1, 2 and 3) based on its richness with Adeler classification method. The differences in the grade of blood flow in liver tumors were compared between CDFI and MFI. With respect to the presented morphology, the blood flow was further classified into five types (Type I, …II, III, IV and V). The morphological differences in blood flow shown by MFI between malignant and benign hepatic tumors were then analyzed. RESULTS: For the total 81 lesions, MFI detected 61 lesion cases (75.31%) with blood flow grade 2 and 3, which obviously outperformed CDFI which detected 28 cases (34.57%) of grade 2 and 3 (χ 2 = 35.27, P  = 0.000). The MFI also showed that the most common blood flow morphology of HCC is Type-III (21/48, 43.75%) while the hepatic hemangioma (HEM) is mostly presented as Type V (5/10, 50%). Moreover, the grade of blood flow in MFI varied with different pathological subtypes of HCC (χ 2 = 5.610, P  = 0.018). CONCLUSIONS: Compared with traditional CDFI, MFI reveals more blood vessels in liver lesions with clearer view of blood flow distribution. Besides, MFI technology can demonstrate grade of blood flow for various differentiation stages of malignant liver tumors. Show more

Keywords: Micro-flow imaging (MFI), liver, tumor, vascular, color Doppler flow imaging

DOI: 10.3233/CH-180532

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

Authors: Kremer, Antje | Wußmann, Maximiliane | Herrmann, Marietta | Raghunath, Michael | Walles, Heike

Article Type: Research Article

Abstract: BACKGROUND: Prolyl hydroxylase inhibitors (PHIs) are promising compounds to promote angiogenesis by stabilizing hypoxia-inducible factor-1α (HIF-1α ), a master regulator of angiogenesis. Increased HIF-1α presence induces expression of proangiogenic genes such as vascular endothelial growth factor (VEGF). OBJECTIVE: We investigated the pharmacological induction of hypoxia via the PHI ciclopirox olamine (CPX) as angiogenesis strategy on human dermal microvascular endothelial cell (hd-mvEC) spheroids directly and indirectly via activating human mesenchymal stem cells (hMSCs). METHODS: HMSCs were isolated from bone marrow and hd-mvECs from foreskin biopsies. MSC-conditioned medium after CPX stimulation (MSC-CM CPX) was analyzed by …VEGF ELISA and Proteome Profiler™ Human Angiogenesis Array. Direct stimulation with CPX and indirect stimulation via MSC-CM CPX were compared in sprouting assays of hd-mvEC spheroids. RESULTS: Direct stimulation with CPX significantly increased sprouting of hd-mvEC spheroids. MSC-CM CPX also induced sprouting from hd-mvEC spheroids, which was mediated by angiogenic VEGF and other proangiogenic factors that had been produced by stimulated hMSCs. CONCLUSIONS: The stimulation with CPX increased the proangiogenic response of hd-mvECs and hMSCs. The direct stimulation of hd-mvECs with CPX has the potential to replace external VEGF supplementation. Thus, CPX can induce angiogenesis in ECs even in the absence of auxiliary cells demonstrating a promising proangiogenic approach. Show more

Keywords: HIF-1α, prolyl hydroxylase inhibitor, ciclopirox olamine, mesenchymal stem cells, endothelial cells, sprouting, angiogenesis, vascularization

DOI: 10.3233/CH-190559

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Martini, Romeo

Article Type: Research Article

Abstract: Critical limb Ischemia (CLI) is the most advanced stage of peripheral arterial disease. It is clinically defined as rest pain with or without skin ulcer or gangrene and carries a very poor prognosis with a high rates of limb amputation and cardiovascular mortality. Despite the first definition of CLI has been published more than 30 years ago, the debate about what it really is, is still open. Over the years he hemodynamic parameters utilised to define the critical level of limb perfusion have changed. This has raised some question about the apparent confusion about the definition of CLI. Moreover, a …new term such as “limb threatening ischemia” has replaced the definition of CLI in recent guideline. Therefore, it becomes necessary to understand the evolution of the concept and the definition of CLI to understand the future trend. Hence this work analysing the guideline documents on peripheral arterial disease that have defined the CLI to date, aiming to clarify the path that has brought to the current conceptual changes of the definition of CLI. Show more

DOI: 10.3233/CH-190576

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2019

Authors: Yang, Yancheng | Che, Yuanyuan | Yang, Likun

Article Type: Research Article

Abstract: OBJECTIVE: To analyze the relationship of the serum levels of inflammatory cytokines with the degree of anemia and vascular endothelial function in children with systemic lupus erythematosus (SLE), as well as to explore the predictive value of risk factors for SLE in children. METHODS: A total of 88 patients with SLE diagnosed in the Pediatric Department of our hospital from March 2015 to February 2017 were selected as the observation group, and 30 healthy controls with comparable age were selected as the control group. Basic characteristics of all enrolled individuals, such as age, sex, height and weight, and …the related biochemical indexes, including the levels of inflammatory cytokines [C-reactive protein (CRP), tumor necrosis factor α (TNF-α ), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR)], blood routine test including hemoglobin (Hb), platelet (PLT) and mean corpuscular volume as well as related indexes of vascular endothelial function, such as homocysteine (Hcy), carbonic oxide (NO), endothelial nitric oxide synthase (eNOS) were measured. In addition, the SLE disease activity index (SLEDAI) score of patients was also recorded. RESULTS: There were no significant differences regarding age, sex, body mass index (BMI), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) between observation group and control group (p  >  0.05), but the total cholesterol (TC) level in observation group was significantly higher than that in control group (p  <  0.05). In addition, the levels of CRP, TNF-α , IL-6 and ESR in serum in observation group were significantly higher than those in control group (p  <  0.05). However, the Hb, PLT and mean corpuscular volume in observation group were significantly lower than those in control group (p  <  0.05). Moreover, the levels of Hcy, NO and eNOS in observation group were significantly higher than those in control group (p  <  0.05). Furthermore, correlation analyses showed that CRP was positively correlated with SLEDAI score (r  = 0.791, p  <  0.001) and Hcy level (r  = 0.817, p  <  0.001), but negatively correlated with Hb level (r  = –0.663, p  <  0.001). CONCLUSION: There is a close relationship between serum inflammatory cytokines and SLE severity, Hcy or Hb level in children, suggesting these inflammatory cytokines might be novel indicators for evaluating the severity of SLE. Show more

Keywords: Children, systemic lupus erythematosus, inflammatory cytokine, anemia, vascular endothelial function

DOI: 10.3233/CH-180492

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

Authors: Shin, Eun-Seok | Chung, Ju-Hyun | Park, Seung Gu | Saleh, Ahmed | Lam, Yat-Yin | Bhak, Jong | Jung, Friedrich | Morita, Sumio | Brachmann, Johannes

Article Type: Research Article

Abstract: BACKGROUND: Exercise electrocardiography (ECG) is frequently used as a diagnostic measure in patients with suspected coronary artery disease (CAD). However, it has low sensitivity for the detection of CAD. Magnetocardiography (MCG) has been proposed as an alternative tool to accurately diagnose CAD. OBJECTIVE: To date, a direct comparison of MCG to ECG has not been performed. This study sought to compare them for predicting the presence of significantly obstructive CAD. METHODS: The patients with chest pain or other symptoms suggestive of CAD were enrolled in the analysis. All the patients underwent a clinical evaluation, exercise ECG, …MCG test, and coronary angiography (CA). CAD was defined as stenosis ≥70% in at least one major coronary artery on quantitative analysis of CA. RESULTS: We prospectively enrolled 202 consecutive patients who suggested CAD. The prevalence of CAD on CA was 39.1%. Sensitivity and accuracy for CAD diagnosis was higher for MCG compared with exercise ECG (sensitivities 68.4% and 40.5%, p <0.001, specificities 95.1% and 91.1%, p = 0.267, and accuracies 84.7% and 71.3%, p <0.001, respectively). There was no incremental diagnostic value of combined MCG and ECG to detect coronary artery disease (p = 0.357). CONCLUSIONS: For the patients with intermediate to high risk of CAD, MCG exercise test provides better diagnostic accuracy for the detection of relevant obstruction of the epicardial coronaries when directly compared to exercise ECG. Show more

Keywords: Electrocardiography, magnetocardiography, diagnostic performance

DOI: 10.3233/CH-180485

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

Authors: Peng, Shiyun | Ding, Hong | Fu, Tiantian | Wang, Bengang | Wang, Wenping | Zhou, Jinzhu

Article Type: Research Article

Abstract: BACKGROUND: Savitzky-Golay filter is a digital filter used in data smoothing, we introduced a contrast-enhanced ultrasound (CEUS) quantification software based on the filter (SGCQ). OBJECTIVE: To explore the methodology of analyzing hepatic tumors hemodynamics applying SGCQ software and the correlation between SGCQ parameters and hepatocellular carcinoma (HCC) angiogenesis. METHODS: Nighty-seven right-lobe located hepatic mass cases (15 females and 82 males, mean age 58±10y, mean lesion size: 39.9±11.6 mm) underwent CEUS scan preoperatively and had a final diagnosis of HCC (n  = 52) or colorectal cancer metastatic liver tumors (MLT, n  = 45) were included. CEUS was carried out using …a 1–5 MHz convex probe. The CEUS clips were recorded and analyzed off-line to obtain the parameters. The parameters were analyzed by 3 observers separately to investigate inter-observer variability. Parameters were compared between tumor and adjacent liver and between different tumors. Immunohistochemistry was used to evaluate the microvessel density (MVD) of HCC, and the correlation between the parameters and MVD was analyzed. RESULTS: Intraclass correlation coefficient (ICC) of all parameters were greater than 0.75 except wash-in slope (a3) and time to peak (TTP) of adjacent liver. The parameters of a3, wash-out slope (a2), perfusion time (PT) and area under the curve (AUC) were significantly different between HCC and liver. The a2, a3, AUC, PT and enhanced intensity (EI) were significantly different between MLT and liver. AUC, a2, a3, da1 and dPI were significantly different between HCC and MLT. AUC, a2 and EI correlated with MVD. CONCLUSION: SGCQ software quantification have good consistency among three observers, the parameters of SGCQ can display the hemodynamics of HCC and MLT and the difference between them. AUC and EI can serve as useful biomarkers in tumor angiogenesis evaluation. Show more

Keywords: Contrast-enhanced ultrasound, Savitzky-Golay filter, methodology, hepatocellular carcinoma, colorectal cancer, neovascularization

DOI: 10.3233/CH-180432

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-170347

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