Clinical Hemorheology and Microcirculation

The cold ischemia –reperfusion injury may lead to microcirculatory disturbances, hepatocellular swelling, inflammation, and organ dysfunction. Nicorandil is an anti-ischemic, ATP-sensitive potassium (KATP) channel opener drug and has proved its effectiveness against hepatic Ischemia/Reperfusion (I/R) injury.

This study aimed to investigate the effect of Nicorandil on mitochondrial apoptosis, oxidative stress, inflammation, histopathological changes, and cold ischemic tolerance of the liver in an ex vivo experimental isolated-organ-perfusion model.

We used an ex vivo isolated rat liver perfusion system for this study. The grafts were retrieved from male Wistar rats (n = 5 in each), preserved in cold storage (CS) for 2 or 4 hours (group 1, 2), or perfused for 2 or 4 hours (group 3, 4) immediately after removal with Krebs Henseleit Buffer (KHB) solution or Nicorandil containing KHB solution under subnormothermic (22–25°C) conditions (group 5, 6). After 15 minutes incubation at room temperature, the livers were reperfused with acellular, oxygenated solution under normothermic condition for 60 minutes.

In the Nicorandil perfused groups, significantly decreased liver enzymes, GLDH, TNF-alpha, and IL-1ß were measured from the perfusate. Antioxidant enzymactivity was higher in the perfused groups. Histopathological examination showed ameliorated tissue deterioration, preserved parenchymal structure, decreased apoptosis, and increased Bcl-2 activity in the Nicorandil perfused groups.

Perfusion with Nicorandil containing KHB solution may increase cold ischemic tolerance of the liver via mitochondrial protection which can be a potential therapeutic target to improve graft survival during transplantation.

To compare the diagnostic value of shear wave elastography (SWE), fine needle aspiration (FNA) and BRAF gene detection (BRAF^V600E gene mutation detection) in ACR TI-RADS 4 and 5 thyroid nodules.

SWE images, FNA cytological results and BRAF detection results of ACR TI-RADS 4 and 5 thyroid nodules confirmed by pathology were analyzed retrospectively. The receiver operating characteristic (ROC) curve was drawn to determine the best cutoff value of SWE Emax. In the combined diagnosis of SWE, FNA and BRAF, firstly, the nodules with BRAF gene mutation were included in the positive ones, secondly, the nodules with benign and malignant FNA were included in the FNA + SWE or FNA + SWE + BRAF negative and positive ones respectively, finally, for FNA uncertain nodules: those whose SWE Emax were less than or equal to the cutoff value were included in FNA + SWE or FNA + SWE + BRAF negative ones, and those whose SWE Emax were greater than the cutoff value were included in positive ones. The diagnostic efficacy of SWE, FNA, SWE + FNA, FNA + BRAF and their combination in ACR TI-RADS 4 and 5 thyroid nodules were compared.

The ROC curve showed that the best cutoff value of SWE Emax was 40.9 kpa, and the area under ROC curve (AUC) was 0.842 (0.800∼0.885). The sensitivity, specificity and accuracy of SWE were 76.3% (270/354), 75.5% (80/106) and 76.1% (350/460), respectively. The sensitivity, specificity and accuracy of FNA were 58.2% (206/354), 88.7% (94/106) and 65.2(300/460), respectively. The sensitivity, specificity and accuracy of FNA + BRAF were 95.5% (338/354), 88.7% (94/106) and 93.9% (432/460), respectively. The sensitivity, specificity and accuracy of SWE + FNA were 85.9% (304/354), 98.1% (104/106) and 88.7% (408/460), respectively. The sensitivity, specificity and accuracy of SWE + FNA + BRAF were 98.3% (348/354), 98.1% (104/106) and 98.3% (452/460), respectively. For the diagnostic accuracy, SWE + FNA + BRAF > FNA + BRAF > FNA + SWE > SWE > FNA, the difference was statistically significant (all P > 0.05).

For ACR TI-RADS 4 and 5 thyroid nodules, SWE and FNA have high diagnostic efficiency. For the diagnostic accuracy, FNA + BRAF is better than FNA + SWE. FNA combination with BRAF gene detection further improves the diagnostic sensitivity and accuracy of FNA. The combined application of the three is the best.

To thoroughly evaluate preoperative risk factors for deep venous thrombosis (DVT) in patients with knee rheumatoid arthritis (RA) undergoing unilateral total knee arthroplasty (TKA).

Clinical data of 106 patients with knee RA who underwent unilateral TKA from August 2014 to October 2020 were collected. All patients received ultrasonic examination of the veins of both lower extremities on the third day after TKA and were divided into DVT and non-DVT groups. The associations between age, gender, body mass index (BMI), history of diabetes/hypertension, common serum lipid levels, indicators related to coagulation function, blood viscosity, erythrocyte sedimentation rate (ESR) and postoperative DVT were statistically compared and analyzed.

ESR was significantly correlated with DVT risk after TKA (OR = 1.844, 95% CI = 1.022–2.981, P = 0.019). Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off point of ESR for predicting DVT was 42 mm/h with a sensitivity of 95.5% and specificity of 66.7%.

An increased preoperative ESR value is a risk factor for DVT in patients with knee RA following unilateral TKA. Pre-surgery control of ESR level and prevention of postoperative DVT in these patients are worthy of attention.

Ultrasound-guided fine-needle aspiration (US-FNA) is the most accurate method for preoperative diagnosis of thyroid nodules, but how to deal with false negative results?

This study aimed to find preoperative diagnosis methods including Conventional Ultrasound (CUS), Shear Wave Elastography (SWE) and BRAF V600E testing to differentiate false negative nodules.

Forty-nine nodules in 49 patients with benign FNA results and pathological diagnoses were included. CUS and SWE features were evaluated. BRAF V600E analysis was performed after FNA. Diagnostic performances of three methods were analyzed in predicting malignancy in benign FNA results.

Twenty-seven of 49 nodules were malignant, and 22 nodules were benign. Hypoechogenicity, taller-than-wider, irregular boundary, microcalcification, SWE max, SWE mean and BRAF V600E mutation were risk factors for malignancy. All 7 malignant nodules with BRAF V600E mutations and 18 of 20 malignant nodules without BRAF V600E mutations have two or more suspicious CUS features. Six of 7 malignant nodules with BRAF V600E mutations and 16 of 20 malignant nodules without BRAF V600E mutations had SWE mean value greater than the cut-off value.

CUS, SWE and BRAF V600E were diagnostic tools for malignancy in FNA benign nodules. Further clinical decisions should be considered for nodules with two or more suspicious CUS features and SWE parameters greater than cut-off values whether BRAF V600E is mutational or not.

we have examined the concentration of serum uric acid and the serum uric acid/creatinine ratio as well as their correlations with the main determinants of the hemorheological profile in a group of subjects with subclinical carotid atherosclerosis.

we evaluated the concentration of serum uric acid and the serum uric acid/creatine ratio in 43 men and 57 women [median age 66.00 (25)] with subclinical carotid atherosclerosis, subsequently divided according to the number of traditional cardiovascular risk factors and to the insulin resistance degree.

serum uric acid, but not the serum uric acid/creatinine ratio, results strongly influenced by the number of cardiovascular risk factors and by the insulin resistance degree. In the whole group and in the subgroups of subclinical carotid atherosclerosis subjects, serum uric acid and serum uric acid/creatinine ratio show significant correlation, besides with whole blood viscosity, with plasma viscosity and erythrocyte aggregation. The influence of the serum uric acid on the erythrocyte aggregability that is a part of the erythrocyte aggregation is to ascribe to the action carried out by serum uric acid on the erythrocyte zeta potential.

it is reasonable to think that the treatment of the asymptomatic or symptomatic hyperuricemia with the urate-lowering therapy that reduces the serum uric acid concentration may reflect on the hemorheological profile which role on the atherosclerotic cardiovascular disease is well known.

To examine whether contrast-enhanced ultrasound (CEUS) parameters in patients with advanced pancreatic cancer could be used to assess response to treatment with pulsed-wave high intensity focused ultrasound (PW-HIFU).

We prospectively recorded the pretreatment and posttreatment CEUS related parameters, CA19-9, pain scores of 30 patients with advanced pancreatic cancer treated with PW-HIFU treatment. Correlation of clinical parameters, tumor characteristics, and PW-HIFU treatment energy with CEUS parameters were analyzed.

Pain score decreased after treatment (from 4.80±2.14 to 3.28±1.93, p = 0.001). CA19-9 dropped in RT decreased group, 4 weeks after one session PW-HIFU, compared with prolonged group (p = 0.013). According to the display of blood vessels in the mass by CEUS, tumors were classified by vessel grade (VG), VG1: no vessel can be seen; VG 2: vessels diameter < 5 mm; VG 3: vessels diameter > 5 mm. VGs were different between increased and decreased relative rise intensity (rRI) groups (p = 0.008). VG1 group shown a decreased rRI after treatment, while VG3 group showed the opposite trend (p = 0.006).

CEUS can evaluating response to PW-HIFU in advanced pancreatic cancer. Quantitative analysis may help to assess the short-term efficacy of patients and help for individualized treatment.

To investigate the value of contrast-enhanced ultrasound (CEUS) for the diagnosis of cervical tuberculous lymphadenitis (CTL).

The cohort study included 203 consecutive patients diagnosed with cervical lymph node. Before pathological or laboratory confirmation, all patients underwent CEUS examination, and the imaging findings were analyzed afterward. The diagnostic efficiency of the CEUS imaging findings of CTL was evaluated.

Nighty-seven patients of the 203 (47.8%) were pathologically or laboratory confirmed with a CTL diagnosis while the remainder (52.2%) were diagnosed with non-tuberculous lymphadenitis. Regarding the imaging findings of CEUS, it was more common in CTL patients to find a pattern of heterogeneous enhancement inside the lymph nodes relative to non-tuberculous patients [81.44% (79/97) vs 15.09% (16/106), P < 0.01]. The sensitivity of the feature in diagnosis for CTL was 81.44% and the specificity was 84.91%, resepectively. Furthermore, a pattern of peripheral rim-like enhancement had been notable in CTL patients compared with non-tuberculous patients [86.60% (84/97) vs 12.26% (13/106), P < 0.01], associating with a diagnostic sensitivity of 86.60% and a specificity of 87.74%. When it came to the combination of both imaging findings mentioned above, the features were more prominent in CTL patients than compared with non-tuberculous patients [74.23% (72/97) vs 5.66% (6/106), P < 0.01], with a diagnostic sensitivity of 74.23% and a high specificity of 94.34%. Regarding area under curve (AUC) for the ROC analysis, the feature of internal heterogeneous enhancement, peripheral rim-like enhancement, and both features were 0.832, 0.872, and 0.843.

CEUS patterns of heterogeneous enhancement and peripheral rim-like enhancement of lymph nodes are helpful characteristics for the diagnosis of CTL.

Almost 95% of the venous valves are micron scale found in veins smaller than 300μm diameter. The fluid dynamics of blood flow and transport through these micro venous valves and their contribution to thrombosis is not yet well understood or characterized due to difficulty in making direct measurements in murine models.

The unique flow patterns that may arise in physiological and pathological non-actuating micro venous valves are predicted.

Computational fluid and transport simulations are used to model blood flow and oxygen gradients in a microfluidic vein.

The model successfully recreates the typical non-Newtonian vortical flow within the valve cusps seen in preclinical experimental models and in clinic. The analysis further reveals variation in the vortex strengths due to temporal changes in blood flow. The cusp oxygen is typically low from the main lumen, and it is regulated by systemic venous flow.

The analysis leads to a clinically-relevant hypothesis that micro venous valves may not create a hypoxic environment needed for endothelial inflammation, which is one of the main causes of thrombosis. However, incompetent micro venous valves are still locations for complex fluid dynamics of blood leading to low shear regions that may contribute to thrombosis through other pathways.

To establish and to evaluate a machine learning radiomics model based on grayscale and Sonazoid contrast enhanced ultrasound images for the preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients.

100 cases of histopathological confirmed HCC lesions were prospectively included. Regions of interest were segmented on both grayscale and Kupffer phase of Sonazoid contrast enhanced (CEUS) images. Radiomic features were extracted from tumor region and region containing 5 mm of peritumoral liver tissues. Maximum relevance minimum redundancy (MRMR) and Least Absolute Shrinkage and Selection Operator (LASSO) were used for feature selection and Support Vector Machine (SVM) classifier was trained for radiomic signature calculation. Radiomic signatures were incorporated with clinical variables using univariate-multivariate logistic regression for the final prediction of MVI. Receiver operating characteristic curves, calibration curves and decision curve analysis were used to evaluate model’s predictive performance of MVI.

Age were the only clinical variable significantly associated with MVI. Radiomic signature derived from Kupffer phase images of peritumoral liver tissues (kupfferPT) displayed a significantly better performance with an area under the receiver operating characteristic curve (AUROC) of 0.800 (95% confidence interval: 0.667, 0.834), the final prediction model using age and kupfferPT achieved an AUROC of 0.804 (95% CI: 0.723, 0.878), accuracy of 75.0%, sensitivity of 87.5% and specificity of 69.1%.

Radiomic model based on Kupffer phase ultrasound images of tissue adjacent to HCC lesions showed an observable better predictive value compared to grayscale images and has potential value to facilitate preoperative identification of HCC patients at higher risk of MVI.