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BackgroundThe unfavourable side-effects of late-stage pancreatic cancer treatments call for non-toxic and effective therapeutic approaches. We compared the overall survival (OS) of patients receiving an extract of Viscum album [L.] (VaL) or no antineoplastic therapy.MethodsThis is a prospective, parallel, open label, monocentre, group-sequential, randomised phase III study. Patients with locally advanced or metastatic cancer of the pancreas were stratified according to a binary prognosis index, composed of tumour stage, age and performance status; and were evenly randomised to subcutaneous injections of VaL extracts or no antineoplastic therapy (control). VaL was applied in a dose-escalating manner from 0.01mg up to 10mg three times per week. Patients in both groups received best supportive care. The primary end-point was 12-month OS, assessed in a group-sequential analysis.FindingsWe present the first interim analysis, including data from 220 patients. Baseline characteristics were well balanced between the study arms. Median OS was 4.8 for VaL and 2.7months for control patients (prognosis-adjusted hazard ratio, HR=0.49; p

We tested whether or not heart rate variability (HRV) changes can serve as early signs of ventricular tachycardia (VT) and predict slow and fast VT in patients with an implantable cardioverter defibrillator (ICD).We studied the ICD stored 1000 beat-to-beat intervals before the onset of VT (131 episodes) and during a control time without VT (74 series) in 63 chronic heart failure ICD patients. Standard HRV parameters as well as two nonlinear parameters, namely 'Polvar10' from symbolic dynamics and the finite time growth rates 'Fitgra9' were calculated. Comparing the control and the VT series, no linear HRV parameter showed a significant difference. The nonlinear parameters detected a significant increase in short phases with low variability before the onset of VT (for time series with less than 10% ectopy, P0.05). Subdividing VT into fast (cycle lengthor=270 ms) and slow (270 ms) events, we found that the onset of slow VT was characterized by a significant increase in heart rate, whereas fast VT was triggered during decreased heart rates, compared to the control series.Our data may permit the development of automatic ICD algorithms based on nonlinear dynamic HRV parameters to predict VT before it starts. Furthermore, they may facilitate improved prevention strategies.

Assessment of fluctuations in heart rate (HR) following a premature ventricular complex (PVC) is valuable for identifying patients at high risk of sudden cardiac death. We hypothesised that postextrasystolic potentiation is the main determinant of the regulation patterns of blood pressure (BP) and HR following a PVC. Twelve patients with idiopathic dilated cardiomyopathy (IDC) and 13 control subjects with single PVCs (comparable coupling intervals) were investigated. Non-invasive finger arterial BP and ECGs were analysed. Regulation patterns following a single PVC were quantified using the indices postextrasystolic amplitude potentiation (PEAP) and maximum turbulence slope of five consecutive mean BP values (MBP-TS), and compared with the HR turbulence parameters turbulence slope (HR-TS) and turbulence onset (HR-TO). PEAP was significantly higher in IDC patients compared to controls (48.7 +/- 32.6 vs. 9.8 +/- 5.4 %, P < 0.01), whereas MBP-TS was lower (0.97 +/- 0.60 vs. 2.07 +/- 1.04 mmHg BBI(-1) (BBI, beat-to-beat interval), P < 0.05), as was HR-TS (8.46 +/- 7.90 vs. 30.73 +/- 22.90 ms BBI(-1), P < 0.01). HR-TO was significantly higher in IDC patients (-0.56 +/- 2.19 vs. -5.52 +/- 4.13 %, P < 0.01). In addition, the regulation patterns of BP and HR following a single PVC differed significantly between IDC patients and controls. Specifically, we observed pronounced PEAPs in IDC patients. The baroreflex response initiated by the low pressure amplitude of the PVC was suppressed in IDC patients due to the augmented potentiation of the first postextrasystolic blood pressure. Furthermore, IDC patients displayed impressive postextrasystolic pulsus alternans phenomena, whereas healthy subjects exhibited a typical baroreflex pattern. The pulsus alternans phenomenon seems to be triggered by a PVC.

evic´ SUMMARY Background: The treatment of cancer patients with mistletoe extract is said to prolong their survival and, above all, improve their quality of life. We studied whether the quality of life of patients with advanced pancreatic cancer could be improved by mistletoe extract. Method: An open, single-center, group-sequential, randomized phase III trial (ISRCTN70760582) was conducted. From January 2009 to December 2010, 220 patients with locally advanced or metastatic pancreatic cancer who were receiving no further treatment for pancreatic cancer other than best supportive care were included in this trial. They were stratified by prognosis and randomly allocated either to a group that received mistletoe treatment or to one that did not. Mistletoe extract was given in escalating doses by subcutaneous injection three times a week. The planned interim evaluation of data from 220 patients indicated that mistletoe treatment was associated with longer overall survival, and the trial was terminated prematurely. After termination of the study, the results with respect to quality of life (assessed with the QLO-C30 scales of the European Organisation for Research and Treatment of Cancer) and trends in body weight were evaluated. Results: Data on quality of life and body weight were obtained from 96 patients treated with mistletoe and 72 control patients. Those treated with mistletoe did better on all 6 functional scales and on 7 of 9 symptom scales, including pain (95% confidence interval [CI] �29 to –17), fatigue (95% CI –36.1 to –25.0), appetite loss (95% CI �51 to �36.7), and insomnia (95% CI –45.8 to –28.6). This is reflected by the trend in body weight during the trial.

Heart rate variability is a relevant predictor of cardiovascular risk in humans. However, to use heart and blood pressure (BP) variability or baroreflex sensitivity as markers for hypertensive pregnancy disorders, it is first necessary to describe these parameters in normal pregnancy. To accommodate the complexities of autonomic cardiovascular control we added parameter domains of nonlinear dynamics to conventional linear methods of time and frequency domains. The BP of 27 women with normal pregnancy and 14 nonpregnant women were monitored at a high resolution (200 Hz sampling frequency) using a Portapres for 30 min. The pregnant women were divided into groups of 32 or less or greater than 32 weeks of gestation. Pregnant and nonpregnant women were classified into subclasses of maternal age of less than 28 or 28 or more years. Except for two single parameter domains, we found no significant differences in heart rate and BP variability for pregnant women with different gestational age or different maternal age. Moreover, no significant differences in spontaneous baroreflex sensitivity could be found between pregnant women regardless of either their age or gestational age. In contrast, all measures of nonlinear dynamics of heart rate variability as well as all parameter domains of spontaneous baroreflex sensitivity showed significant changes between pregnant and nonpregnant women, whereas BP variability did not differ between those groups. This complex assessment of autonomic cardiovascular regulation has shown that the parameters tested are stable in the second half of normal pregnancy, and might have the potential to be excellent indicators of pathophysiologic conditions.

This study was designed to improve the prognostic value of heart rate variability (HRV) in patients with dilated cardiomyopathy (DCM) using a new method of long-term symbolic dynamics. DCM patients show a decreased HRV in comparison to healthy subjects (p 27% group (p

In this study heart rate variability (HRV) analysis was applied to characterize patients suffering from coronary heart disease (CHD), dilated cardiomyopathy (DCM) and patients who had survived an acute myocardial infarction (MI). On the basis of several HRV parameters, an optimal discrimination between the different kinds of cardiovascular diseases and between the diseases and healthy controls (HC) was derived by feature selection and linear classification. For each task a small favourable subset of a set of 33 potentially interesting HRV measures was selected with the intention of improving the diagnostic value and facilitating the physiological interpretation of HRV analysis. Time- and frequency-domain parameters as well as parameters from non-linear dynamics were included in the analysis. With the expectation that different diseases are characterized by different phenomena, feature selection was applied for each task separately. Using the features optimal for one task to another task can reveal a loss in performance, but it turned out that one specific parameter set (set1: normalized low frequency LF/P and a non-linear variability measure WPSUM13) was applicable for all tasks, where diseased and healthy subjects have to be distinguished, without significant reduction in performance. This set seems to be a general marker for pathologic changes in HRV and might be used for early detection of heart diseases. The classification between different heart diseases requires another parameter set (set2: meanNN and sdaNN, reflecting the steady state behaviour of the heart rate and long and short term SEAR describing the spectral composition). However, the use of set1 for the separation of different kinds of diseases, where set2 is appropriate, led to significant reduction in performance and vice versa. This observation may be important for future developments of HRV measures especially suitable for the assessment of disease severity. Copyright © 2002 John Wiley & Sons, Ltd.

Standard parameters of heart rate variability are restricted in measuring linear effects, whereas nonlinear descriptions often suffer from the curse of dimensionality. An approach which might be capable of assessing complex properties is the calculation of entropy measures from normalised periodograms. Two concepts, both based on autoregressive spectral estimations are introduced here. To test the hypothesis that these entropy measures may improve the result of high risk stratification, they were applied to a clinical pilot study and to the data of patients with different cardiac diseases. The study shows that the entropy measures discussed here are useful tools to estimate the individual risk of patients suffering from heart failure. Further, the results demonstrate that the combination of different heart rate variability parameters leads to a better classification of cardiac diseases than single parameters.

Background Circulating tumor cells (CTCs) are detectable in peripheral blood of metastatic breast cancer patients (MBC). In this paper we evaluate a new CTC separation method based on a combination of anti-EpCAM- and anti-cytokeratin magnetic cell separation with the aim to improve CTC detection with low target antigen densities. Methods Blood samples of healthy donors spiked with breast cancer cell line HCC1937 were used to determine accuracy and precision of the method. 10 healthy subjects were examined to evaluate specificity. CTC counts in 59 patients with MBC were measured to evaluate the prognostic value on overall survival. Results Regression analysis of numbers of recovered vs. spiked HCC1937 cells yielded a coefficient of determination of R2 = 0.957. The average percentage of cell recovery was 84%. The average within-run coefficient of variation for spiking of 185, 85 and 30 cells was 14%. For spiking of 10 cells the within-run CV was 30%. No CTCs were detected in blood of 10 healthy subjects examined. A standard threshold of 5 CTC/7.5 ml blood as a cut-off point between risk groups led to a highly significant prognostic marker (p Conclusions We show that our CTC detection method is feasible and leads to accurate and reliable results. Our data suggest that a refined differentiation between patients with different CTC levels is reasonable.