Challenging single- and multi-probesets gene expression signatures of pathological complete response to neoadjuvant chemotherapy in breast cancer: experience of the REMAGUS 02 phase II trial.

This study was designed to identify predictive signatures of pathological complete response (pCR) in breast cancer treated by taxane-based regimen, using clinicopathological variables and transcriptomic data (Affymetrix Hgu133 Plus 2.0 devices). The REMAGUS 02 trial (n = 153,training set) and the publicly available M.D. Anderson data set (n = 133, validation set) were used. A re-sampling method was applied. All predictive models were defined using logistic regression and their classification performances were tested through Area Under the Curve (AUC) estimation. A stable set of 42 probesets (31 genes) differentiate pCR or no pCR samples. Single-or 2-probesets signatures, mainly related to ER pathway, were equally predictive of pCR with AUC greater then 0.80. Models including probesets associated with ESR1, MAPT, CA12 or PIGH presented good classification performances. When clinical variables were entered into the model, only CA12 and PIGH, remained informative (p = 0.05 and p = 0.005) showing that a combination of a few genes provided robust and reliable prediction of pCR.

Assessing the reliability of four severity scales depicting skin ageing features.

BACKGROUND: Photographic severity scales depicting facial wrinkling are used extensively to assess the severity of skin ageing features, but they have been poorly investigated for their reproducibility. OBJECTIVES: To investigate the reproducibility of ordinal scales depicting four skin ageing features illustrated by reference photographs. METHODS: A set of 253 images of caucasian women's faces was evaluated independently by four dermatologists using four different skin ageing severity scales: Larnier's overall photodamage, expression lines, glabellar frown lines, and wrinkles under the eyes. For each pair of dermatologists, degree of agreement was estimated using the weighted kappa statistic and degrees of distinguishability between adjacent categories along these scales were estimated using a recently developed log-linear method. RESULTS: The kappa statistic highlighted substantial degrees of agreement between dermatologists for the glabellar frown lines scale, and the log-linear method did not evidence any scale defect. For the three other scales, only fair to moderate degrees of agreement were observed between dermatologists. In addition, difficulties in distinguishing between some adjacent categories were evidenced. CONCLUSIONS: The glabellar frown lines scale is a reproducible tool for assessment of the severity of facial wrinkling. The other scales should be redefined to improve their reproducibility, and therefore their quality, in future studies.

Histological scoring of fibrosis and activity in HIV-chronic hepatitis B related liver disease: performance of the METAVIR score assessed on virtual slides.

BACKGROUND: The METAVIR score, which is the most widely used score in France, was specifically elaborated and evaluated in chronic hepatitis C and has never been validated in HIV-hepatitis virus B (HBV) co-infected patients. AIMS: To validate the use of the METAVIR scoring system for activity and fibrosis on liver biopsies in co-infected HIV-HBV patients. METHODS: METAVIR scoring for activity and fibrosis was first conducted on both original and virtual slides by one pathologist for comparison. Then 55 biopsies turned into virtual slides were scored by three pathologists independently. RESULTS: The scoring comparison between virtual slides and glass slides showed an almost perfect agreement for fibrosis (weighted kappa (kappa(w)) 0.8) and a substantial agreement for activity (kappa(w) 0.68). The inter-observer agreement on virtual slides was moderate to almost perfect (kappa(w) 0.52 to 0.84) for fibrosis and was dependent on the pair of pathologists considered. The best agreement was obtained in scoring advanced fibrosis and cirrhosis versus significant fibrosis versus no or mild fibrosis (kappa(w) 0.70 to 0.84). The agreement for cirrhosis was rated moderate to substantial (kappa(w) 0.54 to 0.79). Agreement for activity was substantial (kappa(w) 0.66 to 0.8). CONCLUSIONS: This study validates the use of virtual slide technology to assess fibrosis and activity on liver biopsies. It also validates the use of the METAVIR score in co-infected HIV-HBV patients and illustrates the challenges in establishing the histological diagnosis of cirrhosis in the HIV-HBV context.

Protective effect of glove on median nerve compression in the carpal tunnel.

OBJECTIVES: To determine the protective effect of gel padded glove on median nerve compression in the carpal tunnel. METHODS: Median nerve conduction parameters, skin temperature, laser Doppler flowmetry and pain modifications were measured during and after a 30-min carpal tunnel external compression protocol performed with and without glove in a random order on six healthy volunteers. RESULTS: Compression induced a rapidly reversible increase in sensory and motor distal latencies, a decrease in sensory amplitude, finger laser Doppler flowmetry and hand skin temperature supporting the hypothesis of a reversible conduction block of ischemic origin. There was no statistical difference between the tests (with or without glove) except for pain that was significantly reduced by glove protection. CONCLUSION: Gel padded glove does not seem to have a protective effect on the carpal tunnel syndrome induced by compression but provides significant comfort.