Reconstruction of standard 12-lead electrocardiograms from 12-lead electrocardiograms recorded with the Mason-Likar electrode configuration

Electrocardiograms (ECGs) made with Mason-Likar electrode configuration (ML-ECGs) show well-known differences from standard 12-lead ECGs (Std-ECGs). We recorded, simultaneously, Std-ECGs and ML-ECGs in 180 subjects. Using these ECGs, 8 × 8 individual and general conversion matrices were created by linear regression, and standard ECGs were reconstructed from ML-ECGs using these matrices. The performance of the matrices was assessed by the root mean square differences between the original Std-ECGs and the reconstructed standard ECGs, by the differences in major ECG parameters, and by comparison of computer-generated diagnostic statements. As a result, we conclude that, based on the root mean square differences, reconstructions with 8 × 8 individual matrices perform significantly better than reconstructions with the group matrix and perform equally well with respect to the calculation of major electrocardiographic parameters, which gives an improved reliability of the QRS frontal axis and the maximal QRS and T amplitudes. Both types of matrices were able to reverse the underdiagnosis of inferior myocardial infarctions and the erroneous statements about the QRS frontal axis that arose in the ECGs that were made by using the Mason-Likar electrode positions.     

Positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose in oncology

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is considered to be a very useful adjunct to anatomic imaging techniques and is now primarily used for oncological indications. These indications include diagnosis, staging, and therapy monitoring. In this review, we discuss the articles in which FDG-PET is clinically used for monitoring therapy in lung and colorectal tumours, head and neck cancer, sarcoma, and hepatocellular carcinoma. It is found that the amount of FDG uptake strongly correlates with response to therapy: a decrease in FDG uptake after therapy indicates a positive response to therapy. However, this conclusion is based on small numbers of patients, whereas the exact response mechanism is still unknown. Moreover, in these case series, the interval between tumour therapy and FDG-PET, as well as the method of quantification, SUV or tumour-to-non-tumour ratios, differ per study. Finally, dynamic imaging is a recommended technique by some authors, but it is not a standard technique in clinical practice to evaluate tumour therapy. Therefore, further study is required which has to deal with these major issues before it is possible to draw definite conclusions.     

Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study

Aims/hypothesis

Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes.

Methods

We measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case–control studies of prevalent (n = 4925) and incident (n = 4277) diabetes. The data were analysed using regression models with adjustment for potential confounders.

Results

There were dynamic changes in metabolite levels in response to the different secretagogues. Furthermore, several fasting pairwise metabolite ratios were associated with one or multiple clamp-derived measures of insulin secretion (all p < 9.2 × 10^?7). These associations were significantly stronger compared with the individual metabolite components. One of the ratios, valine to phosphatidylcholine acyl-alkyl C32:2 (PC ae C32:2), in addition showed a directionally consistent positive association with OGTT-derived measures of insulin secretion and resistance (p ≤ 5.4 × 10^?3) and prevalent type 2 diabetes (OR_{Val_PC ae C32:2} 2.64 [β 0.97 ± 0.09], p = 1.0 × 10^?27). Furthermore, Val_PC ae C32:2 predicted incident diabetes independent of established risk factors in two epidemiological cohort studies (HR_{Val_PC ae C32:2} 1.57 [β 0.45 ± 0.06]; p = 1.3 × 10^?15), leading to modest improvements in the receiver operating characteristics when added to a model containing a set of established risk factors in both cohorts (increases from 0.780 to 0.801 and from 0.862 to 0.865 respectively, when added to the model containing traditional risk factors + glucose).

Conclusions/interpretation

In this study we have shown that the Val_PC ae C32:2 metabolite ratio is associated with an increased risk of type 2 diabetes and measures of insulin secretion and resistance. The observed effects were stronger than that of the individual metabolites and independent of known risk factors.

     

Elucidation of the spatial ventricular gradient and its link with dispersion of repolarization.

The ventricular gradient, a notion conceived by Wilson et al during the 1930s, has contributed considerably to a better understanding of the ECG manifestations of the cardiac repolarization process. The power of the ventricular gradient is its ability to assess the primary factors that contribute to the T wave (i.e., heterogeneity of action potential morphology throughout the ventricles) in the presence of secondary factors contributing to the T wave (i.e., heterogeneity in ventricular depolarization instants). Where T-wave morphology is an ECG expression of heterogeneity of the repolarization, the ventricular gradient discriminates between primary or secondary causes of such heterogeneity. Besides the spatial ventricular gradient (Burger's three-dimensional elaboration of Wilson's two-dimensional concept), body surface mapping of local components of the ventricular gradient has emerged as a technique for assessing local ventricular action potential duration heterogeneity. The latter is believed to contribute to localization of arrhythmogenic areas in the heart. The spatial ventricular gradient, which can be computed on the basis of a regular routine ECG and does not require body surface mapping, aims to assess the overall heterogeneity of ventricular action potential morphology. This review addresses the nature and diagnostic potential of the spatial ventricular gradient. The main focus is the role of the spatial ventricular gradient in ECG assessment of dispersion of repolarization, a key factor in arrhythmogeneity.     

Repetitive lifting and spinal shrinkage, effects of age and lifting technique

The assumed advantages of the so-called leg-lifting technique over the back-lifting technique are still the subject of much debate. The present study was aimed at studying the consequences of performing both lifting techniques on net lumbar moments and spinal shrinkage. Furthermore, the relation between age and spinal shrinkage was studied. Five subjects approximately 40 years old and six subjects 20 years old performed six 5-min bouts of repetitive lifting using each technique on a separate day. Net lumbar moments were calculated using a two-dimensional dynamic linked segment model. Spinal shrinkage was measured at T₁₂ and at the head after each bout of lifting and every 5 min during 1 h preceding the lifting bouts. The peak moments were marginally but significantly higher in the leg-lift. No differences in mean moments and shrinkage between lifting techniques were found. The shrinkage after the back-lift was more pronounced in the older subjects and a similar tendency was found after the leg-lift. The creep rate, i.e. the rate at which the shrinkage approaches its equilibrium was higher in the older subjects. No clear relations of anthropometrical variables and net moments with shrinkage was found. The common advice of using a leg-lift rather than a back-lift was not supported by the present study. Both the mechanical load on the low back (net moments) and the resulting shrinkage show considerable interindividual variation, the causes of which need further elucidation.

The leg-lifting technique is still widely advocated, thought its merits from a biomechanical point of view have been questioned. In this study spinal shrinkage and lumbar moments calculated by means of a dynamic linked segment model are used to compare the leg-lift to the more commonly used back-lift.     

Digital mammography screening: weighing reduced mortality against increased overdiagnosis

Objective

Digital mammography has been shown to increase the detection of ductal carcinoma in situ (DCIS) compared to screen-film mammography. The benefits and risks of such an increase were assessed.

Methods

Breast cancer detection rates were compared between 502,574 screen-film and 83,976 digital mammograms performed between 2004 and 2006 among Dutch screening participants. The detection rates were then modeled using a baseline model and two extreme models that respectively assumed a high rate of progression and no progression of preclinical DCIS to invasive cancer. With these models, breast cancer mortality and overdiagnosis were predicted.

Results

The DCIS detection rate was significantly higher at digital mammography (1.2 per 1000 mammograms (95% C.I. 1.0-1.5)) than at screen-film mammography (0.7 per 1000 mammograms (95% C.I. 0.6-0.7)). Consequently, 287 (range progressive- non progressive model: 1-598) extra breast cancer deaths per 1,000,000 women (a 4.4% increase) were predicted to be prevented. An extra 401 (range: 165-2271) cancers would be overdiagnosed (a 21% increase).

Conclusion

Modeling predicted that digital mammography screening would further reduce breast cancer mortality by 4.4%, at a 21% increased overdiagnosis rate. The consequences of digital screening, however, are sensitive to underlying assumptions on the natural history of DCIS.     

Interpreting overdiagnosis estimates in population-based mammography screening

Estimates of overdiagnosis in mammography screening range from 1% to 54%. This review explains such variations using gradual implementation of mammography screening in the Netherlands as an example. Breast cancer incidence without screening was predicted with a micro-simulation model. Observed breast cancer incidence (including ductal carcinoma in situ and invasive breast cancer) was modeled and compared with predicted incidence without screening during various phases of screening program implementation. Overdiagnosis was calculated as the difference between the modeled number of breast cancers with and the predicted number of breast cancers without screening. Estimating overdiagnosis annually between 1990 and 2006 illustrated the importance of the time at which overdiagnosis is measured. Overdiagnosis was also calculated using several estimators identified from the literature. The estimated overdiagnosis rate peaked during the implementation phase of screening, at 11.4% of all predicted cancers in women aged 0-100 years in the absence of screening. At steady-state screening, in 2006, this estimate had decreased to 2.8%. When different estimators were used, the overdiagnosis rate in 2006 ranged from 3.6% (screening age or older) to 9.7% (screening age only). The authors concluded that the estimated overdiagnosis rate in 2006 could vary by a factor of 3.5 when different denominators were used. Calculations based on earlier screening program phases may overestimate overdiagnosis by a factor 4. Sufficient follow-up and agreement regarding the chosen estimator are needed to obtain reliable estimates.