Real-Time Detection of Markers in Blood.

The real-time selective detection of disease-related markers in blood using biosensors has great potential for use in the early diagnosis of diseases and infections. However, this potential has not been realized thus far due to difficulties in interfacing the sensor with blood and achieving transparent circuits that are essential for detecting of target markers (e.g., protein, ions, etc.) in a complex blood environment. Herein, we demonstrate the real-time detection of a specific protein and ion in blood without a skin incision. Complementary metal-oxide-semiconductor technology was used to fabricate silicon micropillar array (SiMPA) electrodes with a height greater than 600 µm, and the surface of the SiMPA electrodes was functionalized with a self-assembling artificial peptide (SAP) as a receptor for target markers in blood, i.e., cholera toxin (CTX) and mercury(II) ions (Hg). The detection of CTX was investigated in both in vitro (phosphate-buffered saline and human blood serum, HBO model) and in vivo (mouse model) modes via impedance analysis. In the in vivo mode, the SiMPA pierces the skin, comes into contact with the blood system, and creates comprehensive circuits that include all the elements such as electrodes, blood, and receptors. The SiMPA achieves electrically transparent circuits and, thus, can selectively detect CTX in the blood in real time with a high sensitivity of 50 pM and 5 nM in the in vitro and in vivo modes, respectively. Mercury(II) ions can also be detected in both the in vitro and the in vivo modes by changing the SAP. The results illustrate that a robust sensor that can detect a variety of molecular species in the blood system in real time that will be helpful for the early diagnosis of disease and infections.

Worse outcome of sorafenib therapy associated with ascites and Child-Pugh score in advanced hepatocellular carcinoma.

BACKGROUND AND AIM: The outcomes of sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC) and impaired liver function remain unresolved. Although Child-Pugh (CP) classification is widely used for patient categorization, heterogeneity within a given CP class makes outcomes less predictable. The aim was to investigate the prognostic significance of CP score elements on the outcome of sorafenib in patients with advanced HCC and impaired liver function. METHODS: Of 1385 consecutive patients with advanced HCC in our center between January 2007 and December 2010, we reviewed the medical records of 325 patients who received sorafenib monotherapy. RESULTS: Median duration of sorafenib was 2.0 months (range 0.4-24.2) and median follow-up was 4.9 months (range 0.5-43.4). Disease control rates were significantly higher in CP class A (CPA) than in CP class B (CPB) patients. Median overall survival (OS) was 5.8 months. Subgroups with different CP scores showed significantly different OS (months): CPA5, 8.4; CPA6, 5.1; CPB7, 3.5; CPB8-9, 2.6 (P < 0.001). The presence of ascites was a significant prognostic factor in CPB7 patients (hazard ratio 2.262; P = 0.016). OS of CPB7 patients without ascites was similar to that of CPA6 patients (4.6 months) and was significantly longer than that of CPB7 patients with ascites (2.5 months; P = 0.027). OS of CPB7 patients with ascites was similar to that of CPB8-9 patients. CONCLUSIONS: CP score was more important than CP class in predicting the outcome of sorafenib therapy in patients with advanced HCC. Among the CP score components, presence of ascites was a significant prognostic factor, especially in CPB7 patients.