Bart Mertens

Serum protein profiling in mice: Identification of Factor XIIIa as a potential biomarker for muscular dystrophy

Protein profiling in blood serum by fractionation and MS analysis has been applied in mice to assess its applicability as a fast, economical alternative to current DNA and RNA analyses for diagnosis of neuromuscular disorders. Mass spectra of peptides and proteins were generated using serum from dystrophin‐deficient mdx and control mice by WCX ClinProt bead fractionation, followed by MALDI‐MS. Double cross‐validatory linear discriminant and logistic regression data analysis methods were compared with a new Bayesian logistic regression method. These were evaluated on their ability to discriminate between healthy and dystrophic samples, and to identify the discriminatory peaks in the mass spectra. All three approaches classified the spectra with comparable misclassification rates (between 18.4 and 20.6%), with much overlap between the differential peaks identified between the methods. The differential peak pattern from the Bayesian method was sparser and easier to interpret than from the other two methods, without compromising classifying strength. One of the two main differentiating peaks at m/z 3908 was identified as an N‐terminal peptide of coagulation Factor XIIIa, previously identified in human serum. This work underlines the translational aspect of serum protein profiling in mice and supports a further study with serum from patients with neuromuscular disorders.

Inclusion of emergency department patients in early stages of sepsis in a quality improvement programme has the potential to improve survival: a prospective dual-centre study

Study objective Sepsis quality improvement programmes typically focus on severe sepsis (ie, with acute organ failure). However, quality of ED care might be improved if these programmes included patients whose progression to severe sepsis could still be prevented (ie, infection without acute organ failure). We compared the impact on mortality of implementing a quality improvement programme among ED patients with a suspected infection with or without acute organ failure. Methods This prospective observational study among ED patients hospitalised with suspected infection was conducted in two hospitals in the Netherlands. After stratification by sepsis category (with or without organ failure), in-hospital mortality was compared between a full compliance (all quality performance measures achieved) and an incomplete compliance group. Multivariable logistic regression analysis was used to quantify the impact of full compliance on in-hospital mortality, adjusting for disease severity, disposition and hospital. Results There were 1732 ED patients and 130 deaths. Full compliance was independently associated with approximately two-thirds reduction in the odds of hospital mortality (adjusted OR of 0.30 (95% CI 0.19 to 0.47), which was similar in patients with and without organ failure. Among the 1379 patients with suspected infection without acute organ failure, there were 64 deaths, 15 (1.1%) in the full compliance group and 49 (3.6%) in the incomplete compliance group (mortality difference 2.5% (95% CI 1.6% to 3.3%)). Among 353 patients with organ failure, there were 66 deaths, 12 (3.4%) in the full compliance compared with 54 (15.3%) in the incomplete compliance group (mortality difference 11.9% (95% CI 8.5% to 15.3%)). Thus, there was a difference of 76 deaths between full and incomplete compliance groups, and 34 (45%) who benefited were those without acute organ failure. Conclusions Sepsis quality improvement programmes should incorporate ED patients in earlier stages of sepsis given the potential to reduce in-hospital mortality among this population.

Organizing a Competition on Clinical Mass Spectrometry Based Proteomic Diagnosis

This paper gives a description of the structure of the classification competition on mass spectrometry proteomic data which is presented in this issue. All steps according to which the competition was run, leading up to the joint meeting, are explained. The paper gives further details on the data analyzed by all participants. This includes information on the preprocessing steps carried out, with references to appropriate sources describing algorithms used, dimensionalities, definition of calibration and validation sets, sample and group sizes and a description of which data and information was made available to participants. The paper starts with a review of mass spectrometry proteomics from a statistical and bioinformatic viewpoint. We conclude with a discussion on the nature of the competition and some of the decisions made in implementing it.

Impact of QRS complex duration and morphology on left ventricular reverse remodelling and left ventricular function improvement after cardiac resynchronization therapy

To evaluate the impact of the interaction of QRS duration and morphology on left ventricular (LV) reverse remodelling and LV functional improvement in heart failure (HF) patients treated with cardiac resynchronization therapy (CRT).

International Competition on Mass Spectrometry Proteomic Diagnosis

This editorial describes a special issue of Statistical Applications in Genetics and Molecular Biology that presents a full report on an international competition on mass spectrometry proteomic diagnosis, recently organised at the Leiden University Medical Centre in The Netherlands.