Copeptin - a biomarker of short-term mortality risk (7 days) in patients with end-stage liver disease.

Background For many patients with end-stage liver disease, liver transplantation represents the only curative therapy. Transplant recipients are scored and ranked using the model for end-stage liver disease (MELD/MELD-Na). Circulatory impairment is known to deteriorate outcomes; however, it is not incorporated into the current allocation system's score. The aim of our study is to analyze the predictive value of copeptin as a biomarker of circulatory impairment and increased short-term mortality risk in patients with end-stage liver disease. Methods We conducted a retrospective observational study of 615 patients with end-stage liver disease. Patients were recruited using assessments performed during the evaluation process for liver transplantation. Copeptin values were analyzed in comparison to MELD-Na, interleukin 6 (IL-6), and C-reactive protein (CRP). Results Elevated levels of copeptin, IL-6 and CRP, as well as high MELD-Na scores, were significantly correlated with mortality. In a comparison of copeptin-tertiles, patients in group T3 (16.3 pmol/L or more) showed a significantly higher mortality risk (hazard ratio 11.2, p < 0.001). After adjusting for MELD-Na, copeptin remains an independent predictor of mortality. It shows its greatest prognostic strength in short-term mortality, where it performs comparable to MELD-Na (AUROC for 7 day-mortality, 0.941/0.939; p = 0.981) and shows an additional predictive value to MELD-Na for short-term mortality (7 days, p: 0.046; 30 days, p: 0.006). Conclusions Copeptin presents a valuable individual biomarker in detecting patients at risk for short-term mortality. Further studies should be performed to confirm our findings.

Stress biomarkers in minimally invasive and conventional colorectal resections.

INTRODUCTION: Any surgical procedure develops a stress situation for the patient, which can modulate the individual outcome. At present, there is only limited information about stress response in colorectal resections by laparoscopic compared to conventional surgery. Therefore, our objectives were the feasibility and the investigation of stress biomarkers including copeptin and steroid hormones before, during and after colorectal surgery. METHODS: Eleven patients underwent minimally invasive and ten patients conventionally open colorectal surgery. Blood samples were collected before, during and 24 h after surgery and copeptin, NT-proBNP, cortisol, cortisone, interleukin-6 and glucose were analyzed. RESULTS: Both, minimally invasive and conventional-open colorectal surgery caused a fast but heterogeneous response of stress biomarkers. However, the postoperative decrease of cortisol, cortisone and glucose differed between both groups. The stress biomarkers decreased faster down to baseline after minimally invasive surgery, while in open surgery cortisol, cortisone and glucose did not return to baseline within 24 h after operation. CONCLUSIONS: We show in this feasibility study for the first time an increase of copeptin in combination with glucocorticoids as stress biomarkers by open surgery compared to minimally invasive procedures in patients undergoing colorectal surgery. Exceeding an individual threshold of 'stress burden' may have unfavorable effects on the long-time clinical outcome.

The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany.

BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. METHODS/DESIGN: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. DISCUSSION: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Influencing Factors and Differences in Born Aggregometry in Specialized Hemostaseological Centers: Results of a Multicenter Laboratory Comparison.

Introduction Light transmission aggregometry (LTA) is regarded as the gold standard in platelet function diagnostics. However, there is a relevant degree of interlaboratory variability in practical applications. Objective The aim of the present study was to develop a practicable laboratory comparison on LTA and to analyze differences and influencing factors in regard to standardization in five specialized hemostaseological centers. Methods The study was performed on 30 patients in total. Each center performed LTA on blood samples from six healthy volunteers (three men and three women) using the inductors collagen (Col), adenosine diphosphate (ADP), arachidonic acid (ARA), and ristocetin. The LTA was performed three times using different methods as follows: (1) International Society on Thrombosis and Haemostasis recommendations with identical reagents, (2) in-house protocols and the identical reagents; and (3) in-house protocols and in-house reagents. Results A total of 396 measurements of 30 probands were performed. Even after standardization of the protocol and using identical reagents, there were significant differences between the centers regarding the final and maximum aggregation ( p = 0.002 and <0.001) and further significant differences in the maximum and final aggregation according to the wavelength of the device used to measure the LTA (PAP-8: 430 nm, APACT 4004: 740 nm [ p < 0.001 each]). Using identical reagents but individual inductor concentrations and laboratory protocols also resulted in different maximum and final aggregation. The largest differences were seen with Col and ristocetin; there were significant influences from the reagents' manufacturers in the results of aggregometry for the inductor Col ( p < 0.01) but not for ADP, ARA, and ristocetin. Conclusion In this study, we proved that there are significant influences from the used aggregometers, inductors concentrations, and manufacturers. These results illustrate the challenges and importance of standardization of LTA.

Biomarkers for Non-Invasive Stratification of Coronary Artery Disease and Prognostic Impact on Long-Term Survival in Patients with Stable Coronary Heart Disease.

Knowledge about cardiac and inflammatory biomarkers in patients with stable coronary artery disease (CAD) is limited. To address this, we analyzed 3072 patients (36% female) with a median follow-up of 10 years in the Leipzig LIFE Heart Study with suspected CAD with coronary angiography. Selected biomarkers included troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, C-reactive protein (hsCRP), and interleukin-6 (IL-6). Patients were stratified by CAD severity: CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis < 50%), and CAD2 (≥one stenosis ≥ 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2; GC2: CAD0 vs. CAD1 + 2. CAD0, CAD1, and CAD2 were apparent in 1271, 631, and 1170 patients, respectively. Adjusted for classical risk factors, hs-cTnT, NT-proBNP, and IL-6 differed significantly in both GC and hsCRP only in GC2. After multivariate analysis, hs-cTnT, NT-proBNP, and IL-6 remained significant in GC1. In GC2, hs-cTnT (p < 0.001) and copeptin (p = 0.014) reached significance. Ten-year survival in groups CAD0, CAD1, and CAD2 was 88.3%, 77.3%, and 72.4%. Incorporation of hs-cTnT, NT-proBNP, copeptin, and IL-6 improved risk prediction (p < 0.001). The studied cardiac and inflammatory biomarkers enable fast and precise non-invasive identification of mortality risk in CAD patients, allowing the tailoring of primary and secondary CAD prevention.

Salivary cortisone, as a biomarker for psychosocial stress, is associated with state anxiety and heart rate.

BACKGROUND: Stress activates the central nervous, the autonomic nervous, and the endocrine system. This study aimed to (1) test the usability of salivary cortisone in a standardized psychosocial stressor, (2) create a comprehensive profile of hormonal responses to determine laboratory parameters with high discriminatory power, and (3) analyze their association with psychometric and autonomic stress measures. METHODS: Healthy young men (18-35 years) completed either the Trier Social Stress Test (TSST) (n = 33) or a Placebo-TSST (n = 34). Blood and saliva were collected at 14 time points along with state-anxiety (STAI) and heart rate. Serum steroids (cortisol*, cortisone*, dehydroepiandrosterone-sulfate, androstenedione*, progesterone*, 17-hydroxyprogesterone*, testosterone, estradiol*, aldosterone*), salivary cortisol* and cortisone*, copeptin*, adrenocorticoptropic hormone*, corticosteroid-binding globulin, and salivary alpha-amylase* were analyzed. We used mixed-design ANOVAs to test group differences, receiver operator characteristic (ROC) curve analyses to assess the discriminatory power of each measure, and Spearman correlation analyses to probe the association between measures. RESULTS: The largest area under the ROC curve was observed in salivary cortisone at 20 min after the end of the TSST (AUC = 0.909 ± 0.044, p < 0.0001). Significant time-by-group interactions were found in the parameters marked with * above, indicating stress-induced increases. The peak response of salivary cortisone was significantly associated with those of STAI (rho = 0.477, p = 0.016) and heart rate (rho = 0.699, p < 0.0001) in the TSST group. CONCLUSION: Our study found salivary cortisone to be a stress biomarker with high discriminatory power and significant correlations with subjective and autonomic stress measures. Our results can inform future stress studies of sampling time for different laboratory parameters.