No abstract

The biochemical response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis is a strong predictor of long‐term outcome and thus facilitates the rapid identification of patients needing new therapeutic approaches. Numerous criteria for predicting outcome of treatment have been studied based on biochemical response to UDCA at 1 year. We sought to determine whether an earlier biochemical response at 3 or 6 months could as efficiently identify patients at risk of poor outcome, as defined by liver‐related death, liver transplantation, and complications of cirrhosis. We analyzed the prospectively collected data of 187 patients with a median follow‐up of 5.8 years (range, 1.3‐14 years). The survival rates without adverse outcome at 5 years and 10 years were 86% and 63%. Under UDCA therapy, laboratory liver parameters experienced the most prominent improvement in the first 3 months (P < 0.0001) and then stayed relatively stable for the following months. The Paris, Barcelona, Toronto, and Ehime definitions, but not the Rotterdam definition, applied at 3, 6, and 12 months significantly discriminated the patients in terms of long‐term outcome. Compared with biochemical responses evaluated after 1 year of UDCA therapy, biochemical responses at the third month demonstrated higher positive predictive value (PPV) but lower negative predictive value (NPV) and increased negative likelihood ratio (NLR) by all definitions; biochemical responses at the sixth month showed higher or the same PPV and NPV and lower NLR by all definitions. Conclusion: For the previously published criteria, biochemical responses at the sixth month can be used in place of those evaluated after 1 year of UDCA therapy. Our findings justify a more rapid identification of patients who need new therapeutic approaches. (HEPATOLOGY 2013)

Background Anemia is one of the most common complications of sepsis. Sepsis-related anemia is associated mainly with inflammation. We aimed to observe the changes in the inflammatory anemia-associated parameters of patients with sepsis in the early stage of intensive care unit (ICU) admission and to evaluate their association with 28-day mortality. Methods A total of 198 patients with sepsis were divided into survivor ( n = 110) and non-survivor ( n = 88) groups on the basis of 28-day survival. Healthy volunteers ( n = 20) were enrolled as a control group. Plasma levels of iron, ferritin, erythropoietin (EPO), soluble transferrin receptor (sTfR), hepcidin, interleukin-6 (IL-6), hemoglobin and the red blood cell distribution width (RDW) were measured on days 1, 3 and 7 of ICU admission. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score was calculated. Results Patients with sepsis showed significant decreases in hemoglobin, plasma iron and sTfR/log ferritin and significant increases in plasma EPO, sTfR, hepcidin, ferritin and IL-6 on days 1, 3 and 7 of ICU admission compared with healthy volunteers. Hemoglobin was correlated negatively with plasma IL-6 and hepcidin. In patients with sepsis, non-survivors had significantly lower plasma iron, EPO and sTfR/log ferritin, but higher plasma hepcidin, ferritin and IL-6 than survivors on days 1, 3 and 7 of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality but to a varying extent. In particular, in predicting 28-day mortality, plasma hepcidin had an area under the receiver operating curve of 0.808 and 87.3% specificity, which was the highest among the inflammatory anemia-associated parameters tested. Conclusions Inflammatory anemia-associated parameters changed significantly in patients with sepsis in the first week of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality. Plasma hepcidin might have a superior predictive value, with high specificity, compared with other inflammatory anemia-associated parameters for 28-day mortality of sepsis patients in the ICU. Electronic supplementary material The online version of this article (10.1186/s13613-019-0542-7) contains supplementary material, which is available to authorized users.

Biophysical studies on individual cells can help to establish the relationship between mechanics and biological function. In the case of cancer, mechanical properties of cells have been linked to metastatic activity and disease progression and can be crucial for understanding cellular physiology and metabolism. In this study, we report measurements of the stiffness of breast cancer cells using a novel silicon MEMS resonant sensor and validated the results with atomic force microscopy (AFM). We measured the mass and stiffness of individual benign (MCF-10A), non-invasive malignant (MCF-7), and highly-invasive malignant (MDA-MB-231) breast cancer cells using the silicon resonant MEMS sensors. The sensor extracts the average stiffness value of the whole cell and allows comparison of stiffness of different cell types. We found differences between the cell lines in both elasticity and viscosity, and confirmed our observations through independent measurements with atomic force microscopy (AFM). Coupled with measurements over time, this approach could lead to a multimodal investigation of both growth and physical properties of single cells. The mechanical property sensitivity and resolution of these pedestal sensors were investigated to understand the significance of the frequency shift during operation. The lowest achievable spring constant and damping constant resolutions have a range of 0.06 to 17.10 mN m(-1) and 1.63 to 1.96 nN s m(-1), respectively, measured across the range of physiological cell mechanical properties.