In 33 nivolumab-treated patients, high diastolic WBV before the treatment was also tended to be associated with overall and progression-free survival. High diastolic WBV also predicted poor survival in patients with low alpha-fetoprotein (AFP) and proteins induced by vitamin K antagonist-II (PIVKA-II) levels. Patients with high diastolic WBV had poor survival, and multivariate Cox regression analyses showed high diastolic WBV was an independent risk factor for poor survival with the Child-Pugh B7 and PVTT. Notably, patients who developed extrahepatic metastases during the observation period among patients without metastases at diagnosis had higher diastolic WBV initially. Multivariate logistic regression showed that high diastolic WBV > 16 cP was an independent factor associated with metastases. Systolic WBV and diastolic WBV were significantly increased in patients with metastases compared with patients without metastases. Portal vein tumor thrombosis (PVTT), tumor size, number of tumors, and systolic/diastolic WBV were factors associated with extrahepatic metastases. Extrahepatic metastases were observed in 15 treatment-naïve patients (11.3%) at diagnosis. Systolic and diastolic WBV was measured using an automated scanning capillary tube viscometer at diagnosis or before the nivolumab treatment. This pilot study included a discovery cohort of 148 treatment-naïve HCC patients with preserved liver function, and a validation cohort of 33 treatment-experienced HCC patients with nivolumab. However, relevance of WBV in hepatocellular carcinoma (HCC) remains unclear. Our results are relevant to better characterize SCA, provide useful insights relevant to rheological consequences of blood transfusions, and, more generally, extend to the rheology of mixed suspensions having particles with different rigidities, as well as offering possibilities for developments in the field of soft material composites.Whole blood viscosity (WBV) is increased in cancer patients and associated with the advanced stage with systemic metastases.
Through numerical simulations, we also highlight that most of the viscosity increase of the suspension is due to the rigidity of the particles rather than their sickled or spherical shape. Although aggregation of RBCs is known to affect blood rheology at low shear rates, and our simulations mimic this effect via an adhesion potential, we show that such adhesion, or aggregation, is unlikely to provide a physical rationalization for the viscosity increase observed in the experiments at moderate shear rates due to rigidified cells. Our results show that there is a rheological signature within blood viscosity to clearly identify the fraction of rigidified cells among healthy deformable cells down to a 5% volume fraction of rigidified cells. We also perform systematic numerical simulations of a similar mixed suspension of soft RBCs, rigid particles, and their hydrodynamic interactions. Here, we report systematic experimental measurements of the viscosity of a suspension varying the fraction of rigid particles within a suspension of healthy cells. However, it is unclear how the rigidity of cells is related to the viscosity of blood, in part because SCA patients are often treated with transfusions of variable amounts of normal RBCs and only a fraction of cells will be stiff. It is known that blood from patients with SCA has a higher viscosity than normal blood. In SCA there is an impaired deformability of some cells, which are much stiffer and with a different shape than healthy cells, and thereby affect regular blood flow. Healthy RBCs are highly deformable objects that under flow can penetrate blood capillaries smaller than their typical size. Sickle cell anemia (SCA) is a disease that affects red blood cells (RBCs).
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