A simple clinical assessment is superior to systematic triage in prediction of mortality in the emergency department.

OBJECTIVE: To compare the Danish Emergency Process Triage (DEPT) with a quick clinical assessment (Eyeball triage) as predictors of short-term mortality in patients in the emergency department (ED). METHODS: The investigation was designed as a prospective cohort study conducted at North Zealand University Hospital. All patient visits to the ED from September 2013 to December 2013 except minor injuries were included. DEPT was performed by nurses. Eyeball triage was a quick non-systematic clinical assessment based on patient appearance performed by phlebotomists. Both triage methods categorised patients as green (not urgent), yellow, orange or red (most urgent). Primary analysis assessed the association between triage level and 30-day mortality for each triage method. Secondary analyses investigated the relation between triage level and 48-hour mortality as well as the agreement between DEPT and Eyeball triage. RESULTS: A total of 6383 patient visits were included. DEPT was performed for 6290 (98.5%) and Eyeball triage for 6382 (~100%) of the patient visits. Only patients with both triage assessments were included. The hazard ratio (HR) for 48-hour mortality for patients categorised as yellow was 0.9 (95% CI 0.4 to 1.9) for DEPT compared with 4.2 (95% CI 1.2 to 14.6) for Eyeball triage (green is reference). For orange the HR for DEPT was 2.2 (95% CI 1.1 to 4.4) and 17.1 (95% CI 5.1 to 57.1) for Eyeball triage. For red the HR was 30.9 (95% CI 12.3 to 77.4) for DEPT and 128.7 (95% CI 37.9 to 436.8) for Eyeball triage. For 30-day mortality the HR for patients categorised as yellow was 1.7 (95% CI 1.2 to 2.4) for DEPT and 2.4 (95% CI 1.6 to 3.5) for Eyeball triage. For orange the HR was 2.6 (95% CI 1.8 to 3.6) for DEPT and 7.6 (95% CI 5.1 to 11.2) for Eyeball triage, and for red the HR was 19.1 (95% CI 10.4 to 35.2) for DEPT and 27.1 (95% CI 16.9 to 43.5) for Eyeball triage. Agreement between the two systems was poor (kappa 0.05). CONCLUSION: Agreement between formalised triage and clinical assessment is poor. A simple clinical assessment by phlebotomists is superior to a formalised triage system to predict short-term mortality in ED patients.

Prediction of coronary heart disease or heart failure using high-sensitivity cardiac troponin T: A pilot study.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is a good prognostic marker for mortality. However, it is uncertain if hs-cTnT can be used to detect sub-clinical cardiac disease. METHOD: Pilot study in patients without known heart disease and elevated hs-cTnT measured at presentation to the emergency department. Hs-cTnT was measure with Roche Diagnostics. Echocardiography was used to assess structural heart disease and the participants underwent computed tomography angiography for assessment of coronary artery disease and agatston score. RESULTS: Ten patients were included in the final cohort. Median age was 68 years IQR (57-78) and 80% were female (n = 8). Six patients had a history of chronic obstructive lung disease and five patients had history of hypertension. The median level of hs-cTnT was 26 ng/L and values ranged from 19 ng/L to 495 ng/L. The median calcium score was 12. Three patients had signs of coronary artery disease. All patients had normal left ventricular ejection fraction with a median LVEF at 54.5%. Two patients were noted to have increased left ventricular mass index (LVMI). CONCLUSION: The majority of patients with hs-cTnT above the 99th percentile did not have structural heart disease or ischaemic coronary disease. However, 30% of the patient did have signs of coronary disease and might benefit from preventive medical treatment. Measuring hs-cTnT in the absence of acute illness might be a better approach for evaluation for sub-clinical cardiac disease.

Gender-partitioned patient medians of serum albumin requested by general practitioners for the assessment of analytical stability.

BACKGROUND: Recently, the use of separate gender-partitioned patient medians of serum sodium has revealed potential for monitoring analytical stability within the optimum analytical performance specifications for laboratory medicine. The serum albumin concentration depends on whether a patient is sitting or recumbent during phlebotomy. We therefore investigated only examinations requested by general practitioners (GPs) to provide data from sitting patients. METHODS: Weekly and monthly patient medians of serum albumin requested by GP for both male and female patients were calculated from the raw data obtained from three analysers in the hospital laboratory on examination of samples from those >18 years. The half-range of medians were applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated (females/males). RESULTS: The medians for male and female patients were closely related despite considerable variation due to the current analytical variation. This relationship was confirmed by the calculated half-range for the monthly ratio between the genders of 0.44%, which surpasses the optimum analytical performance specification for bias of serum albumin (0.72%). The weekly ratio had a half-range of 1.83%, which surpasses the minimum analytical performance specifications of 2.15%. CONCLUSIONS: Monthly gender-partitioned patient medians of serum albumin are useful for monitoring of long-term analytical stability, where the gender medians are two independent estimates of changes in (delta) bias: only results requested by GP are of value in this application to ensure that all patients are sitting during phlebotomy.

Separate patient serum sodium medians from males and females provide independent information on analytical bias.

BACKGROUND: During monitoring of monthly medians of results from patients undertaken to assess analytical stability in routine laboratory performance, the medians for serum sodium for male and female patients were found to be significantly related. METHODS: Daily, weekly and monthly patient medians of serum sodium for both male and female patients were calculated from results obtained on samples from the population >18 years on three analysers in the hospital laboratory. The half-range of medians was applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated. RESULTS: The medians of both genders demonstrated dispersions over time, but they were closely connected in like patterns, which were confirmed by the half-range of the ratios of medians for males and females that varied from 0.36% for daily, 0.14% for weekly and 0.036% for monthly ratios over all instruments. CONCLUSIONS: The tight relationship between the gender medians for serum sodium is only possible when raw laboratory data are used for calculation. The two patient medians can be used to confirm both and are useful as independent estimates of analytical bias during constant calibration periods. In contrast to the gender combined median, the estimate of analytical bias can be confirmed further by calculation of the ratios of medians for males and females.

Elevated prostate specific antigen and reduced 10-year survival among a cohort of Danish men consecutively referred from primary care to an urological department during 2005-2006.

It remains unclear whether total prostate specific antigen (tPSA) or complex PSA (cPSA) has the best diagnostic performance. Additionally, the utility of percentage free PSA (%fPSA) is still debated. Our objectives were to compare the diagnostic performances of tPSA, cPSA, and %fPSA among patients referred from GP to an Urological Specialist and to investigate prognostic factors and survival in the cohort. A total of 1261 consecutive male patients without previously known prostate cancer (PCa) were referred to the same Department of Urology during June 2005 to August 2006. Some 299 patients were diagnosed with PCa and 962 patients were found without PCa. Among the PCa patients, the median age, tPSA, cPSA, and %fPSA levels were 70.8 years, 13.4 µg/L, 10.8 µg/L, and 12.6%. For patients without PCa the results were 67.5 years, 2.5 µg/L, 1.9 µg/L, and 24.9%. The sensitivity, specificity, PVpos, PVneg, and efficiency of tPSA and cPSA were overlapping (p > .05). In the tPSA interval >4 µg/L - ≤20 µg/L, %fPSA excluded PCa with a PVneg of 72.4%; 38.5% of PCa patients had a tPSA concentration >20 µg/L at the time of referral and these patients had a reduced 10-year survival as compared to patients with tPSA concentrations ≤20 µg/L. In conclusion, tPSA and cPSA showed similar diagnostic performances. %fPSA provided additional diagnostic information at tPSA concentrations >4 µg - ≤20 µg/L. The high percentage of patients with tPSA concentrations >20 µg/L indicate delayed use of tPSA resulting in advanced disease at presentation and reduced patient survival.

Galectin 3: association to neurohumoral activity, echocardiographic parameters and renal function in outpatients with heart failure.

BACKGROUND: Galectin 3 (Gal-3) reflects cardiac fibrosis in heart failure HF, but has also been associated to renal fibrosis and impaired renal function. Previous research has suggested that Gal-3 could be a cardio-renal biomarker, but it has never been tested simultaneous in a single study whether Gal-3 reflects echocardiographic measures, neurohumoral activity and renal function. The aim of this study was to evaluate the relationship between plasma concentrations of Gal-3 and neurohumoral activity, myocardial and renal function in patients with HF, including advanced echocardiographic measures and 24-h urinary albumin excretion (albuminuria). METHODS: We prospectively enrolled 132 patients with reduced left ventricular ejection fraction (LVEF) referred to an outpatient HF clinic. The patients had a median age of 70 years (interquartile rage: 64-75), 26.5 % were female, median LVEF was 33 % (27-39 %) and 30 % were in NYHA class III-IV. RESULTS: Patients with plasma concentrations of Gal-3 above the median had significantly lower estimated glomerular filtration rate (eGFR) and this association remained significant in multivariate regression analysis (ß: -0.010; 95 % CI -0.012--0.008; P < 0.001), adjusted for age, gender, medical treatment. Plasma concentrations of Gal-3 were not associated with albuminuria (Beta: 0.008; 95 % CI:-0.028-0.045; P = 0.652). There were no association between plasma concentrations of Gal-3 and myocardial function or structure estimated by LVEF, LVmassIndex, LVIDd, E/é or LV global longitudinal strain (P > 0.05 for all). In multivariate analyses plasma concentrations of Gal-3 were significantly associated with the cardiac biomarkers: NT-proBNP (ß: 0.047; 95 % CI: 0.008-0.086; P = 0.020), proANP (ß: 0.137; 95 % CI: 0.067-0.207; P < 0.001), chromogranin A (ß: 0.123; 95 % CI: 0.052-0.194; P < 0.001) and Copeptin (ß: 0.080; 95 % CI: 0.000-0.160; P = 0.049). Multivariate analysis was adjusted for eGFR, age, gender and medical treatment. CONCLUSIONS: Increased plasma concentrations of Gal-3 are associated with reduced eGFR and increased plasma concentrations of NT-proBNP, proANP, chromogranin A and Copeptin, but not with echocardiographic parameters reflecting myocardial function. These results suggest that Gal-3 reflects both increased neurohumoral activity and reduced eGFR, but not myocardial function in patients with systolic HF.

Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer: Updated Guidelines From the European Group on Tumor Markers.

OBJECTIVE: To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer. METHODS: Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. RESULTS: Because of its low sensitivity (50-62% for early stage epithelial ovarian cancer) and limited specificity (94-98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended for the differential diagnosis of a pelvic mass. Because human epididymis protein 4 has been reported to have superior specificity to CA125, especially in premenopausal women, it may be considered either alone or as part of the risk of ovarian malignancy algorithm, in the differential diagnosis of pelvic masses, especially in such women. CA125 should be used to monitor response to first-line chemotherapy using the previously published criteria of the Gynecological Cancer Intergroup, that is, at least a 50% reduction of a pretreatment sample of 70 kU/L or greater. The value of CA125 in posttherapy surveillance is less clear. Although a prospective randomized trial concluded that early administration of chemotherapy based on increasing CA125 levels had no effect on survival, European Group on Tumor Markers state that monitoring with CA125 in this situation should occur, especially if the patient is a candidate for secondary cytoreductive surgery. CONCLUSIONS: At present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin.

Decrease by 50% of plasma IgA tissue transglutaminase antibody concentrations within 2 months after start of gluten-free diet in children with celiac disease used as a confirming diagnostic test.

BACKGROUND: Histological examination of small bowel biopsies is normally the gold standard for the diagnosis of celiac disease (CD). The objective of this study was to investigate whether the rate of decreases in elevated plasma IgA tissue transglutaminase antibody (IgA-tTG) and/or IgG deamidated gliadin peptides antibody (IgG - DGP) concentrations could be used as a confirming test for CD in children on a gluten-free diet (GFD) when biopsy was omitted in the diagnostic process. METHODS: In this retrospective study we compared children (≤18 years old) with a CD-confirming biopsy (n = 16) to children without a biopsy (n = 18). After initiation of GFD the antibody half-life (the time (T½) when the antibody concentration is 50% decreased) was determined in all children. RESULTS: Children with a biopsy (IgA-tTG, T½ = 1.9 months; IgG - DGP, T½ = 2.2 months) and children without a biopsy (IgA-tTG, T½ = 1.6 months; IgG - DGP, T½ = 2.7 months) had comparable T½ (mean) results (p < 0.05) supporting that all children had the CD diagnosis. CONCLUSIONS: When biopsy was omitted a rapid rate of decrease in CD antibody concentrations confirmed the CD diagnosis in children on GFD. The half-lives (T½) of IgA-tTG were less than 2 months in CD children.

Validation of new cancer biomarkers: a position statement from the European group on tumor markers.

BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before initiation of the study. SUMMARY: Application of the methodology outlined above should result in a more efficient and effective approach to the development of cancer biomarkers as well as the reporting of cancer biomarker studies. With rigorous application, all stakeholders, and especially patients, would be expected to benefit.

In vitro detection of circulating tumor cells compared by the CytoTrack and CellSearch methods.

Comparison of two methods to detect circulating tumor cells (CTC) CytoTrack and CellSearch through recovery of MCF-7 breast cancer cells, spiked into blood collected from healthy donors. Spiking of a fixed number of EpCAM and pan-cytokeratin positive MCF-7 cells into 7.5 mL donor blood was performed by FACSAria flow sorting. The samples were shipped to either CytoTrack or CellSearch research facilities within 48 h, where evaluation of MCF-7 recovery was performed. CytoTrack and CellSearch analyses were performed simultaneously. Recoveries of MCF-7 single cells, cells in clusters, and clusters were determined. The average numbers of MCF-7 cells/cells in clusters/clusters recovered from blood by the CytoTrack and CellSearch methods were 103 ± 5.9/27 ± 7.9/11 ± 3.5 (95 % CI) and 107 ± 4.4/20 ± 7.1/10 ± 3.5, respectively, with no difference between the two methods (p = 0.37/p = 0.23/p = 0.09). Overall, the recovery of CytoTrack and CellSearch was 68.8 ± 3.9 %/71.1 ± 2.9 %, respectively (p = 0.58). In spite of different methodologies, CytoTrack and CellSearch found similar number of CTCs, when spiking was performed with the EpCAM and pan cytokeratin-positive cell line MCF-7. The results suggest that CytoTrack and CellSearch have similar abilities to identify CTC in vitro.

Mapping of HLA- DQ haplotypes in a group of Danish patients with celiac disease.

BACKGROUND: A cost-effective identification of HLA- DQ risk haplotypes using the single nucleotide polymorphism (SNP) technique has recently been applied in the diagnosis of celiac disease (CD) in four European populations. The objective of the study was to map risk HLA- DQ haplotypes in a group of Danish CD patients using the SNP technique. METHODS: Cohort A: Among 65 patients with gastrointestinal symptoms we compared the HLA- DQ2 and HLA- DQ8 risk haplotypes obtained by the SNP technique (method 1) with results based on a sequence specific primer amplification technique (method 2) and a technique used in an assay from BioDiagene (method 3). Cohort B: 128 patients with histologically verified CD were tested for CD risk haplotypes (method 1). Patients with negative results were further tested for sub-haplotypes of HLA- DQ2 (methods 2 and 3). RESULTS: Cohort A: The three applied methods provided the same HLA- DQ2 and HLA- DQ8 results among 61 patients. Four patients were negative for the HLA- DQ2 and HLA- DQ8 haplotypes (method 1) but were positive for the HLA- DQ2.5-trans and HLA- DQ2.2 haplotypes (methods 2 and 3). Cohort B: A total of 120 patients were positive for the HLA- DQ2.5-cis and HLA- DQ8 haplotypes (method 1). The remaining seven patients were positive for HLA- DQ2.5-trans or HLA- DQ2.2 haplotypes (methods 2 and 3). One patient was negative with all three HLA methods. CONCLUSIONS: The HLA- DQ risk haplotypes were detected in 93.8% of the CD patients using the SNP technique (method 1). The sensitivity increased to 99.2% by combining methods 1 - 3.

Methylated DNA for monitoring tumor growth and regression: how do we get there?

A wide range of protein cancer biomarkers is currently recommended in international guidelines for monitoring the growth and regression of solid tumors. However, a number of these markers are also present in low concentrations in blood obtained from healthy individuals and from patients with benign diseases. In contrast, evidence has accumulated that suggests that modified methylated DNA is strongly related to the cancer phenotype. The modifications found in modified methylated DNA include a global loss of methylation in the genomes of the tumor cells as well as focal hypermethylation of gene promoters. Because tumor cells naturally secrete DNA and upon cell death leak DNA, modified methylated DNA can be detected in blood, urine, sputum and other body fluids. At present international guidelines do not include recommendations for monitoring modified methylated DNA. The low level of evidence can partly be explained by incomplete collection of serial blood samples, by analytical challenges, and by lack of knowledge of how monitoring studies should be designed and how serial marker data obtained from individual patients should be interpreted. Here, we review the clinical validity and utility of methylated DNA for monitoring the activity of malignant disease.

Design of tumor biomarker-monitoring trials: a proposal by the European Group on Tumor Markers.

A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such monitoring trials. The panel proposes a 4-phase model for biomarker-monitoring trials analogous to that in use for the investigation of new drugs. In phase I, biomarker kinetics and correlation with tumor burden are assessed. Phase II evaluates the ability of the biomarker to identify, exclude, and/or predict a change in disease status. In phase III, the effectiveness of tumor biomarker-guided intervention is assessed by measuring patient outcome in randomized trials. Phase IV consists of an audit of the long-term effects after biomarker monitoring has been included into standard patient care. Systematic well-designed evaluations of biomarkers for monitoring may provide a stronger evidence base that might enable their earlier use in evaluating responses to cancer therapy.

Interpretation of increments in serial tumour biomarker concentrations depends on the distance of the baseline concentration from the cut-off.

BACKGROUND: In the management of breast cancer, several algorithms for interpretation of measured concentrations during monitoring have been introduced, without objective evaluation of their performance regarding the distance of the starting concentration from the cut-off concentration. METHODS: A computer simulation model has developed using parameters for the tumour biomarker CA 15-3 regarding biological variation and different rates of increase during progressive disease. Seven different algorithms, which include the cut-off point in the calculations, are applied to the simulated data corresponding to 1000 surrogate patients. Steady-state variation (CV-within-subject=14.9%) is based on Gaussian random numbers and an exponential increase in tumour growth (λ=0.009, 0.021, and 0.090 kU/day). RESULTS: The main outcome of the simulations was that low starting concentrations (baseline concentrations) delay the detection of progressive disease (true-positive), whereas, baseline concentrations just below the cut-off value results in false-positive results of progression during steady-state situations. The algorithms investigated show varying susceptibility for baseline concentrations approaching the cut-off. Thus, three of the algorithms show > 90% false-positives and three algorithms < 5% false-positives when baseline concentrations were just below the cut-off point. CONCLUSIONS: Based on the simulations, it is possible to select the optimal algorithms for early detection of progressive disease and a low percentage of false-positives.

National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers.

BACKGROUND: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS: Published reports relevant to use of tumor markers for 5 cancer sites--testicular, prostate, colorectal, breast, and ovarian--were critically reviewed. RESULTS: For testicular cancer, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring. alpha-Fetoprotein is also recommended for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign prostatic disease when total PSA is <10 microg/L. In colorectal cancer, carcinoembryonic antigen is recommended (with some caveats) for prognosis determination, postoperative surveillance, and therapy monitoring in advanced disease. Fecal occult blood testing may be used for screening asymptomatic adults 50 years or older. For breast cancer, estrogen and progesterone receptors are mandatory for predicting response to hormone therapy, human epidermal growth factor receptor-2 measurement is mandatory for predicting response to trastuzumab, and urokinase plasminogen activator/plasminogen activator inhibitor 1 may be used for determining prognosis in lymph node-negative patients. CA15-3/BR27-29 or carcinoembryonic antigen may be used for therapy monitoring in advanced disease. CA125 is recommended (with transvaginal ultrasound) for early detection of ovarian cancer in women at high risk for this disease. CA125 is also recommended for differential diagnosis of suspicious pelvic masses in postmenopausal women, as well as for detection of recurrence, monitoring of therapy, and determination of prognosis in women with ovarian cancer. CONCLUSIONS: Implementation of these recommendations should encourage optimal use of tumor markers.

Valid analytical performance specifications for combined analytical bias and imprecision for the use of common reference intervals.

Background Many clinical decisions are based on comparison of patient results with reference intervals. Therefore, an estimation of the analytical performance specifications for the quality that would be required to allow sharing common reference intervals is needed. The International Federation of Clinical Chemistry (IFCC) recommended a minimum of 120 reference individuals to establish reference intervals. This number implies a certain level of quality, which could then be used for defining analytical performance specifications as the maximum combination of analytical bias and imprecision required for sharing common reference intervals, the aim of this investigation. Methods Two methods were investigated for defining the maximum combination of analytical bias and imprecision that would give the same quality of common reference intervals as the IFCC recommendation. Method 1 is based on a formula for the combination of analytical bias and imprecision and Method 2 is based on the Microsoft Excel formula NORMINV including the fractional probability of reference individuals outside each limit and the Gaussian variables of mean and standard deviation. The combinations of normalized bias and imprecision are illustrated for both methods. The formulae are identical for Gaussian and log-Gaussian distributions. Results Method 2 gives the correct results with a constant percentage of 4.4% for all combinations of bias and imprecision. Conclusion The Microsoft Excel formula NORMINV is useful for the estimation of analytical performance specifications for both Gaussian and log-Gaussian distributions of reference intervals.

High-sensitivity cardiac troponin T is superior to troponin I in the prediction of mortality in patients without acute coronary syndrome.

BACKGROUND: Differences in prevalence and prognostic information of cardiac troponin T (cTnT) and I (cTnI) concentrations in patients without acute coronary syndrome (ACS) are insufficiently investigated. High-sensitivity assays (hs-cTn) have led to an increased interest in hs-cTn for risk stratification. Here, we compare hs-cTnT and hs-cTnI in prediction of mortality patients without ACS. METHOD AND RESULTS: Patients aged >18 years, consecutively admitted to an emergency department (ED) were included. Blood was collected at admission and later analyzed with high-sensitivity assays for cTnT (Roche) and cTnI (Siemens). Troponin concentrations were reported as normal or increased according to the clinical cut-off value of 99th percentile as defined by the manufacturer. The primary outcome was all-cause mortality. Of the 822 participants (median, 65 years [48-77]; 428 female [52%]), 239 patients died. Median follow-up time was 3.0 years [2.1-3.0]. Elevation of hs-cTn was observed in 40% (n = 345) for hs-cTnT and 8% (n = 64) for hs-cTnI, p < 0.001. The relationship between elevated hs-cTn and mortality was strong for both hs-cTnT and hs-cTnI [HR 6.0 (95%CI: 2.9-12.6) vs. 5.1 (95%CI: 1.9-13.6)].There was no difference in prognostic accuracy for short-term mortality (30 days) between hs-cTnT and hs-cTnI. However, the prognostic accuracy for long-term mortality (1080 days) was superior for hs-cTnT than for hs-cTnI [area under the receivers operating curve (AUC) 0.81 vs 0.74, p < 0.001]. CONCLUSION: Both hs-cTnI and hs-cTnT were predictive for all-cause mortality. Notably, hs-cTnT measurement showed superior prognostic performance in predicting long-term all-cause mortality compared with hs-cTnI.

Performance of seven criteria to assess CA125 increments among ovarian cancer patients monitored during first-line chemotherapy and the post-therapy follow-up period.

AIM: To investigate seven CA125 criteria to monitor progressive ovarian cancer among patients with stage IC-IV disease. MATERIALS & METHODS: Four criteria were used to asses CA125 increments starting from concentrations ≥35 U/ml and three criteria to asses increments starting from concentrations <35 U/ml. RESULTS: A total of 231 patients were allocated to CA125 monitoring. The performances of the CA125 criteria were similar with sensitivities of 30-55%, negative predictive values of 28-46%, positive predictive values of 90-100% and median lead times of 26-87 days. CONCLUSION: The criteria showed low sensitivity and inability to exclude progressive ovarian cancer. The study suggests that CA125 information cannot stand alone but should be considered used in conjunction with other investigative procedures.

Influence of renal impairment on aldosterone status, calcium metabolism, and vasopressin activity in outpatients with systolic heart failure.

AIMS: Renal dysfunction (RD) is associated with increased morbidity and mortality in heart failure (HF). At present, no specific treatment for patients with RD, to prevent progression of HF, has been developed. How different hormone axes-and thereby potential treatment options-are affected by RD in HF warrants further investigations. METHODS AND RESULTS: Patients with left ventricular ejection fraction (LVEF) <0.45% were enrolled prospectively from an outpatient HF clinic. Glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR), and patients were grouped by eGFR: eGFR group I, ≥90 mL/min/1.73 m2 ; eGFR group II, 60-89 mL/min/1.73 m2 ; and eGFR group III, ≤59 mL/min/1.73 m2 . Multivariate linear regression models were developed to evaluate the associations between eGFR groups and hormones. A total of 149 patients participated in the study. Median age was 69 [interquartile range (IQR): 64-73] and 26% were female; LVEF was 33% (IQR: 27-39), 78% were in functional class II-III, median eGFR was 74 (54-89) mL/min/1.73 m2 , and median N-terminal pro-brain natriuretic peptide was 1303 pg/mL (IQR: 441-2740). RD was associated with increased aldosterone, parathyroid hormone (PTH), and copeptin concentrations (P < 0.05 for all) after adjustment for traditional confounders and medical treatment. CONCLUSIONS: RD is associated with increased concentrations of aldosterone, PTH, and copeptin in systolic HF outpatients. Our results underscore the importance of treatment with mineralocorticoid receptor antagonist in systolic HF in particular in patients with RD and suggest that vasopressin and parathyroid receptor antagonism are potential treatment options in HF patients with known RD.