Proteins are routinely measured in clinical laboratories for diagnosis, prognosis and therapy monitoring. Nevertheless, both test improvements (performance) and innovations (biomarkers) are needed, and protein N-glycosylation offers a rich source of potential markers. Here, we have analyzed the total serum N-glycome in a matched case-control study (124 cases versus 124 controls) of colorectal cancer patients. The results were validated in an independent sample cohort (both 61 cases versus 61 controls) and further tested in post-operative samples of cured patients. Our results revealed significant differences between patients and controls, with increased size (antennae) and sialylation of the N-glycans in the colorectal cancer patient sera as compared to mainly di-antennary N-glycans in sera from controls. Furthermore, glycan alterations showed strong associations with cancer stage and survival: The five-year survival rate largely varied between patients with an altered serum N-glycome (46%) and an N-glycome similar to controls (87%). Importantly, the total serum N-glycome showed prognostic value beyond age and stage. This clinical glycomics study provides novel serum biomarker candidates and shows the potential of total serum N-glycans as a prognostic panel. Moreover, serum N-glycome changes reverted to a control-like profile after successful treatment as was demonstrated from pre- and post-operative samples.

Of contemporary bleeding RS, the CRUSADE score was found to be the most accurate quantitative tool for NSTEACS and STEMI patients undergoing coronary arteriography.

Information on the age at onset distribution of the asymptomatic stage of a disease can be of paramount importance in early detection and timely management of that disease. However, accurately estimating this distribution is challenging, because the asymptomatic stage is difficult to recognize for the patient and is often detected as an incidental finding or in case of recommended screening; the age at onset is often interval-censored. In this paper, we propose a method for the estimation of the age at onset distribution of the asymptomatic stage of a genetic disease based on ascertained pedigree data that take into account the way the data are ascertained to overcome selection bias. Simulation studies show that the estimates seem to be asymptotically unbiased. Our work is motivated by the analysis of data on facioscapulohumeral muscular dystrophy, a genetic muscle disorder. In our application, carriers of the genetic causal variant are identified through genetic screening of the relatives of symptomatic carriers and their disease status is determined by a medical examination. The estimates reveal an early age at onset of the asymptomatic stage of facioscapulohumeral muscular dystrophy.

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