Validation of putative biomarkers of furan exposure through quantitative analysis of furan metabolites in urine of F344 rats exposed to stable isotope labeled furan.

Humans are chronically exposed to furan, a potent liver toxicant and carcinogen that occurs in a variety of heat-processed foods. Assessment of human exposure based on the furan content in foods is, however, subject to some uncertainty due to the high volatility of furan. Biomarker monitoring is thus considered an alternative or complementary approach to furan exposure assessment. Previous work suggested that urinary furan metabolites derived from the reaction of cis-2-butene-1,4-dial (BDA), the reactive intermediate of furan, with glutathione (GSH) or amino acids may serve as potential biomarkers of furan exposure. However, some metabolites were also reported to occur in urine of untreated animals, indicating either background contamination via animal feed or endogenous sources, which may limit their suitability as biomarkers of exposure. The overall aim of the present study was to accurately establish the correlation between external dose and concentration of furan metabolites in urine over time and to discriminate against endogenous formation and furan intake via feed. To this end, the furan metabolites GSH-BDA (N-[4-carboxy-4-(3-mercapto-1H-pyrrol-1-yl)-1-oxobutyl]-L-cysteinylglycine), NAcLys-BDA (R-2-(acetylamino)-6-(2,5-dihydro-2-oxo-1H-pyrrol-1-yl)-1-hexanoic acid), NAcCys-BDA-NAcLys (N-acetyl-S-[1-[5-(acetylamino)-5-carboxypentyl]-1H-pyrrol-3-yl]-L-cysteine) and NAcCys-BDA-NAcLys sulfoxide (N-acetyl-S-[1-[5-(acetylamino)-5-carboxypentyl]-1H-pyrrol-3-yl]-L-cysteine sulfoxide) were simultaneously analyzed by stable isotope dilution ESI-LC-MS/MS as unlabeled and [13C4]-furan dependent metabolites following oral administration of a single oral dose of isotopically labelled [13C4]-furan (0.1, 1, 10, 100 and 1000 µg/kg bw) to male and female F344/DuCrl rats. Although a linear correlation between urinary excretion of [13C4]-furan-dependent metabolites was observed, analysis of unlabeled NAcLys-BDA, NAcCys-BDA-NAcLys and NAcCys-BDA-NAcLys sulfoxide revealed substantial, fairly constant urinary background levels throughout the course of the study. Analysis of furan in animal feed excluded feed as a source for these background levels. GSH-BDA was identified as the only furan metabolite without background occurrence, suggesting that it may present a specific biomarker to monitor external furan exposure. Studies in humans are now needed to establish if analysis of urinary GSH-BDA may provide reliable exposure estimates.

Precision Mass Measurements of Neutron-Rich Scandium Isotopes Refine the Evolution of N=32 and N=34 Shell Closures.

We report high-precision mass measurements of ^{50-55}Sc isotopes performed at the LEBIT facility at NSCL and at the TITAN facility at TRIUMF. Our results provide a substantial reduction of their uncertainties and indicate significant deviations, up to 0.7 MeV, from the previously recommended mass values for ^{53-55}Sc. The results of this work provide an important update to the description of emerging closed-shell phenomena at neutron numbers N=32 and N=34 above proton-magic Z=20. In particular, they finally enable a complete and precise characterization of the trends in ground state binding energies along the N=32 isotone, confirming that the empirical neutron shell gap energies peak at the doubly magic ^{52}Ca. Moreover, our data, combined with other recent measurements, do not support the existence of a closed neutron shell in ^{55}Sc at N=34. The results were compared to predictions from both ab initio and phenomenological nuclear theories, which all had success describing N=32 neutron shell gap energies but were highly disparate in the description of the N=34 isotone.

GDF15 reflects beta cell function in obese patients independently of the grade of impairment of glucose metabolism.

BACKGROUND AND AIMS: Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular morbidity and mortality found to be both marker and target of impaired glucose metabolism. GDF15 increases following glucose administration and is up-regulated in obesity and diabetes. We investigate here the relationship between GDF15 and beta cell function. METHODS AND RESULTS: In this cross-sectional study we evaluated GDF15 concentrations in 160 obese subjects (BMI 35-63 kg/m2, age 39.4 ± 18.6 years, m/f 38/122) who underwent a 75 g oral glucose tolerance test (OGTT). Based on the OGTT results, the cohort was divided into two groups: 1) normal fasting glucose and normal glucose tolerance (n = 80), 2) impaired fasting glucose, impaired glucose tolerance or type 2 diabetes (n = 80). The relationship of GDF15 to fasting and OGTT-based dynamic insulin sensitivity and insulin secretion parameters was evaluated. GDF15 was higher in the prediabetes and diabetes groups and correlated with HbA1c, glucose, insulin as well as baseline and dynamic indices of insulin sensitivity and estimated beta cell function. Multiple regression analysis revealed that age, waist-to-height ratio, glomerular filtration rate and prehepatic beta cell function, but not the grade of impairment of glucose metabolism, were independent predictors of GDF15. Subgroup analysis showed that of all parameters of glucose metabolism only C-peptide, fasting prehepatic beta cell function and insulinogenic index remained significantly related to GDF15 in both groups. CONCLUSION: We conclude that in patients with severe obesity, GDF15 strongly relates to beta cell function and should be further investigated as a potential therapeutic target and biomarker guiding treatment options.

Dawning of the N=32 Shell Closure Seen through Precision Mass Measurements of Neutron-Rich Titanium Isotopes.

A precision mass investigation of the neutron-rich titanium isotopes ^{51-55}Ti was performed at TRIUMF's Ion Trap for Atomic and Nuclear science (TITAN). The range of the measurements covers the N=32 shell closure, and the overall uncertainties of the ^{52-55}Ti mass values were significantly reduced. Our results conclusively establish the existence of the weak shell effect at N=32, narrowing down the abrupt onset of this shell closure. Our data were compared with state-of-the-art ab initio shell model calculations which, despite very successfully describing where the N=32 shell gap is strong, overpredict its strength and extent in titanium and heavier isotones. These measurements also represent the first scientific results of TITAN using the newly commissioned multiple-reflection time-of-flight mass spectrometer, substantiated by independent measurements from TITAN's Penning trap mass spectrometer.

Lost in plasmids: next generation sequencing and the complex genome of the tick-borne pathogen Borrelia burgdorferi.

BACKGROUND: Borrelia (B.) burgdorferi sensu lato, including the tick-transmitted agents of human Lyme borreliosis, have particularly complex genomes, consisting of a linear main chromosome and numerous linear and circular plasmids. The number and structure of plasmids is variable even in strains within a single genospecies. Genes on these plasmids are known to play essential roles in virulence and pathogenicity as well as host and vector associations. For this reason, it is essential to explore methods for rapid and reliable characterisation of molecular level changes on plasmids. In this study we used three strains: a low passage isolate of B. burgdorferi sensu stricto strain B31(-NRZ) and two closely related strains (PAli and PAbe) that were isolated from human patients. Sequences of these strains were compared to the previously sequenced reference strain B31 (available in GenBank) to obtain proof-of-principle information on the suitability of next generation sequencing (NGS) library construction and sequencing methods on the assembly of bacterial plasmids. We tested the effectiveness of different short read assemblers on Illumina sequences, and of long read generation methods on sequence data from Pacific Bioscience single-molecule real-time (SMRT) and nanopore (Oxford Nanopore Technologies) sequencing technology. RESULTS: Inclusion of mate pair library reads improved the assembly in some plasmids as did prior enrichment of plasmids. While cp32 plasmids remained refractory to assembly using only short reads they were effectively assembled by long read sequencing methods. The long read SMRT and nanopore sequences came, however, at the cost of indels (insertions or deletions) appearing in an unpredictable manner. Using long and short read technologies together allowed us to show that the three B. burgdorferi s.s. strains investigated here, whilst having similar plasmid structures to each other (apart from fusion of cp32 plasmids), differed significantly from the reference strain B31-GB, especially in the case of cp32 plasmids. CONCLUSION: Short read methods are sufficient to assemble the main chromosome and many of the plasmids in B. burgdorferi. However, a combination of short and long read sequencing methods is essential for proper assembly of all plasmids including cp32 and thus, for gaining an understanding of host- or vector adaptations. An important conclusion from our work is that the evolution of Borrelia plasmids appears to be dynamic. This has important implications for the development of useful research strategies to monitor the risk of Lyme disease occurrence and how to medically manage it.

Buried free flaps in head and neck reconstruction: higher risk of free flap failure?

Thrombosis of the pedicle is central to free flap failure, and early revision of a compromised flap is the key to successfully salvage a flap. Therefore, the majority of free flaps in reconstructive head and neck surgery are used with the ability to visually examine the flap. Sometimes, due to intra-operative circumstances, it is necessary to use a flap that cannot be monitored externally. These flaps are called buried flaps and have the reputation of being put at risk. The current literature provides only limited data to support or disprove this position. A single institution retrospective review of patient charts between 2007 and 2015 was performed. Flap monitoring was carried out with hand-held Doppler of the pedicle hourly for the first 72 h in all cases. Additional duplex ultrasound was performed in the majority of buried flaps. A total of 437 flaps were included into the study. 37 flaps (7.8 %) were identified to fulfill the criteria of a buried free flap. In total, four patients had complications, three of which required operative reexploration. All interventions were successful, resulting in no flap loss in our series. An accurate operation technique combined with meticulous monitoring protocols supported by duplex ultrasound can result in satisfactory outcome of buried flaps. No enhanced risk of flap loss of buried flaps was found in our cohort.

Measurement of Excitation Spectra in the

Excitation spectra of ^{11}C are measured in the ^{12}C(p,d) reaction near the η^{'} emission threshold. A proton beam extracted from the synchrotron SIS-18 at GSI with an incident energy of 2.5 GeV impinges on a carbon target. The momenta of deuterons emitted at 0° are precisely measured with the fragment separator (FRS) operated as a spectrometer. In contrast to theoretical predictions on the possible existence of deeply bound η^{'}-mesic states in carbon nuclei, no distinct structures are observed associated with the formation of bound states. The spectra are analyzed to set stringent constraints on the formation cross section and on the hitherto barely known η^{'}-nucleus interaction.

Clinical impact of malnutrition on complication rate and length of stay in elective ENT patients: a prospective cohort study.

Malnutrition is considered as an independent risk factor for morbidity, mortality and a prolonged hospital stay for in-hospital patients. While most available data on the impact of malnutrition on health-related and financial implications refer to gastroenterologic or abdominal surgery patients, little is known about the impact of malnutrition on Ear Nose Throat (ENT)/head and neck surgery patients. The objective of this study was to investigate the impact of malnutrition on morbidity and length of hospital stay in an elective ENT/head and neck surgery patient cohort. The study was performed as a single-center, prospective cohort study at a tertiary referral centre. Nutritional risk at admission was assessed using the NRS-2002 screening tool. Multivariate regression models were used to determine independent risk factors for complications and a prolonged hospitalization. Three hundred fifty one participants were included in the study. A malignant disease was found in 62 participants (17.7 %). 62 patients (17.7 %) were at a moderate to severe risk of malnutrition. A bad general health condition and complications during hospital stay could be identified as independent risk factors for a prolonged hospitalization. Patients with a malignant tumor showed a more than fourfold higher risk of developing at least one complication. Malnutrition, however, was not statistically associated with a higher complication rate or a prolonged hospital stay. Our data suggests that malnutrition does not seem to play such an important role as a risk factor for complications and a prolonged hospital stay in ENT patients as it does in other disciplines like abdominal surgery or gastroenterology.

Strong association of serum- and glucocorticoid-regulated kinase 1 with peripheral and adipose tissue inflammation in obesity.

OBJECTIVE: The serum- and glucocorticoid-regulated kinase 1 (SGK1) is an early transcriptional target of glucocorticoids and is activated via insulin. Here we investigate the regulation of SGK1 expression in human obesity, diet-induced murine obesity and human monocytic cell line THP-1 monocytes. SUBJECTS AND METHODS: SGK1 expression was studied in subcutaneous and omental adipose tissue (AT) of 20 morbidly obese and 20 age- and gender-matched non-obese controls in murine diet-induced obesity and the THP-1 cell line. The regulation of SGK1 by inflammatory signals was tested in THP-1 cells. RESULTS: Murine diet-induced obesity is associated with a significant upregulation of Sgk1 in gonadal AT. Sgk1 expression is highest in the macrophage-rich stromal vascular fraction and lower in adipocytes. In humans, AT SGK1 is predominantly expressed in CD14(+) macrophages and significantly upregulated in omental and subcutaneous AT of obese subjects. SGK1 mRNA expression in both omental and subcutaneous AT correlates with body mass index, circulating leptin and C-reactive protein, and the local expression of inflammatory markers including monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. The expression of SGK1 in THP-1 cells is upregulated by inflammatory signals, such as lipopolysaccharide and tumour necrosis factor-α, as well as during the induction of monocyte-to-macrophage maturation. CONCLUSIONS: Our data present the first link between SGK1 and obesity-associated inflammation. SGK1 expression is stimulated in response to inflammatory signals and increased in AT macrophages. The characterisation of SGK1 functions in obesity and immunity may help identify potential therapeutic targets in the treatment of obesity.

Googling caesarean section: a survey on the quality of the information available on the Internet.

OBJECTIVE: To examine the quality and completeness of information on caesarean section in web pages used by laypersons in Brazil, a country with very high rates of caesarean delivery. DESIGN: Cross-sectional study. SETTING: Brazil. SAMPLE: A total of 176 Internet websites. METHODS: The term 'caesarean delivery' and 25 synonyms were entered into the most popular search engines in Brazil. The first three pages of hits were downloaded and assessed by two independent investigators using the DISCERN instrument and a content checklist. MAIN OUTCOME MEASURES: Quality and completeness of information on caesarean section. RESULTS: A total of 3900 web pages were retrieved and 176 fulfilled the selection criteria. The overall average DISCERN score was 43.6 (±8.9 SD), of a maximum score of 75; 30% of the pages were of poor or very poor quality and 47% were of moderate quality. Most pages scored low, especially in questions related to reliability of the information. The most frequently covered topics were: indications for caesarean section (80% of websites), which did not reflect clinical practice; short-term maternal risks (80%); and potential benefits of caesarean section (56%), including maternal and doctor convenience. Less than half of the websites mentioned perinatal risks and less than one-third mentioned long-term maternal risks associated with caesarean section, such as uterine rupture (17%) or placenta praevia/accreta (12%) in future pregnancies. CONCLUSIONS: The quality and completeness of web-based resources in Portuguese about caesarean section were poor to moderate. Pending improvement of these resources, obstetricians should warn pregnant women about these facts and encourage them to discuss what they have read on the Internet about caesarean section. TWEETABLE ABSTRACT: The quality and completeness of information about caesareans is poor in 176 websites used by Brazilians.

[The supraclavicular flap for reconstruction of the head and neck]. / Der supraclaviculäre Lappen zur Rekonstruktion im Kopf-Hals-Bereich.

The complex anatomy of the head and neck region requires the ability to raise a wide spectrum of pedicled and free flaps, to ensure optimal reconstruction of various defects by the reconstructive surgeon. The supraclavicular (island) flap, which has almost been buried in oblivion, provides excellent potential to reconstruct even bigger defects of the head and neck region, while causing minimal donor site morbidity at the same time. Its benefits lie in the reliable skin island and its wide arc of rotation, resulting in excellent cosmetic and functional outcomes.

Diabetes and thrombolysis for acute stroke: a clear benefit for diabetics.

BACKGROUND AND PURPOSE: Diabetes is a predictor for poor outcome after thrombolysis in stroke patients, and early post-stroke glycaemia is associated with higher rates of post-thrombolytic symptomatic intracerebral haemorrhages (SICHs). Diabetic stroke patients may nevertheless profit from thrombolysis. Here, we compared outcome data of matched thrombolysed and non-thrombolysed diabetic and non-diabetic stroke patients from a national database. METHODS: The outcomes of 1079 matched quadruples, each consisting of a thrombolysed diabetic, a non-thrombolysed diabetic, a thrombolysed non-diabetic and a non-thrombolysed non-diabetic case (a total of 4316 cases), enrolled in the Austrian Stroke Unit Registry (2004-2013), were compared. Patients were matched according to sex, age, stroke severity, pre-stroke disability and prior stroke. RESULTS: A regression model with improvement as depending variable found no effect of diabetes (P = 0.158) or the interaction diabetes × thrombolysis (P = 0.507), whereas the effect of thrombolysis itself was highly significant (P < 0.001). Functional outcome (modified Rankin Scale) was significantly better in thrombolysed than in non-thrombolysed diabetic patients at discharge from the stroke-unit (P < 0.001) and 3 months later (P = 0.006). No significant differences were found in the number of SICHs after thrombolytic treatment between diabetic (4.9%) and non-diabetic strokes (3.5%). Both groups had a higher risk of SICH compared with the non-thrombolysed groups (diabetics 2.6%, non-diabetics 2.5%). Due to lack of documentation, the effect of admission blood glucose on SICH was not investigated. CONCLUSIONS: Data from this nationwide survey show that diabetic stroke patients receive a substantial benefit from thrombolysis, and therefore diabetic strokes should not be excluded from thrombolytic treatment.

Utilization of virus φCh1 elements to establish a shuttle vector system for Halo(alkali)philic Archaea via transformation of Natrialba magadii.

In the study described here, we successfully developed a transformation system for halo(alkali)philic members of the Archaea. This transformation system comprises a series of Natrialba magadii/Escherichia coli shuttle vectors based on a modified method to transform halophilic members of the Archaea and genomic elements of the N. magadii virus Ch1. The shuttle vector pRo-5, based on the repH-containing region of Ch1, stably replicated in E. coli and N. magadii and in several halophilic and haloalkaliphilic members of the Archaea not transformable so far. The Ch1 operon ORF53/ORF54 (repH) was essential for pRo-5 replication and was thus identified as the minimal replication origin. The plasmid allowed homologous and heterologous gene expression, as exemplified by the expression of Ch1 ORF3452, which encodes a structural protein, and the reporter gene bgaH of Haloferax lucentense in N. magadii. The new transformation/vector system will facilitate genetic studies within N. magadii and other haloalkaliphilic archaea and will allow the detailed characterization of the gene functions of N. magadii virus Ch1 in their extreme environments.

Quantification noise in single cell experiments.

In quantitative single-cell studies, the critical part is the low amount of nucleic acids present and the resulting experimental variations. In addition biological data obtained from heterogeneous tissue are not reflecting the expression behaviour of every single-cell. These variations can be derived from natural biological variance or can be introduced externally. Both have negative effects on the quantification result. The aim of this study is to make quantitative single-cell studies more transparent and reliable in order to fulfil the MIQE guidelines at the single-cell level. The technical variability introduced by RT, pre-amplification, evaporation, biological material and qPCR itself was evaluated by using RNA or DNA standards. Secondly, the biological expression variances of GAPDH, TNFα, IL-1ß, TLR4 were measured by mRNA profiling experiment in single lymphocytes. The used quantification setup was sensitive enough to detect single standard copies and transcripts out of one solitary cell. Most variability was introduced by RT, followed by evaporation, and pre-amplification. The qPCR analysis and the biological matrix introduced only minor variability. Both conducted studies impressively demonstrate the heterogeneity of expression patterns in individual cells and showed clearly today's limitation in quantitative single-cell expression analysis.

Resistance to the mTOR-inhibitor RAD001 elevates integrin α2- and ß1-triggered motility, migration and invasion of prostate cancer cells.

BACKGROUND: Inhibitors of the mammalian target of rapamycin (mTOR) might become a novel tool to treat advanced prostate cancer. However, chronic drug exposure may trigger resistance, limiting the utility of mTOR inhibitors. METHODS: Metastatic potential of PC3 prostate cancer cells, susceptible (PC3(par)) or resistant (PC3(res)) to the mTOR-inhibitor RAD001 was investigated. Adhesion to vascular endothelium or immobilised collagen, fibronectin and laminin was quantified. Motility, migration and invasion were explored by modified Boyden chamber assay. Integrin α and ß subtypes were analysed by flow cytometry, western blotting and real-time PCR. Integrin-related signalling, EGFr, Akt, p70S6kinase and ERK1/2 activation were determined. RESULTS: Adhesion was reduced, whereas motility, migration and invasion were enhanced in PC3(res). The α2 and ß1 integrin subtypes were dramatically elevated, integrins α1 and α6 were lowered, whereas α5 was nearly lost in PC3(res). Activation of the Akt signalling pathway was strongly upregulated in these cells. Treating PC3(par) cells with RAD001 reduced motility, migration and invasion and deactivated Akt signalling. Blocking studies revealed that α2 and ß1 integrins significantly trigger the motile behaviour of the tumour cells. CONCLUSION: Chronic RAD001 treatment caused resistance development characterised by distinct modification of the integrin-expression profile, driving prostate cancer cells towards high motility.

Sensitive cardiac troponin in the diagnosis and risk stratification of acute heart failure.

BACKGROUND: The aim of our study was to investigate the diagnostic and prognostic value of a sensitive cardiac troponin I (s-cTnI) assay in patients with acute heart failure (AHF). METHODS: Sensitive cardiac troponin I was measured in 667 consecutive patients at presentation to the emergency department with acute dyspnoea. Three s-cTnI strata were predefined: below the limit of detection (<0.01 µg L(-1) , undetectable), detectable but still within the normal range (0.01-0.027 µg L(-1) ) and increased (≥0.028 µg L(-1) , ≥99th percentile). The final diagnosis was adjudicated by two independent cardiologists blinded to the s-cTnI levels. Median follow-up in patients with AHF was 371 days. RESULTS: Levels of s-cTnI were higher in patients with AHF (n = 377, 57%) compared to patients with noncardiac causes of acute dyspnoea (median 0.02 vs. <0.01 µg L(-1) , P < 0.001). In patients with AHF, in-hospital mortality increased with increasing s-cTnI in the three strata (2%, 5% and 14%, P < 0.001). One-year mortality also increased with increasing s-cTnI (21%, 33% and 47%, P < 0.001). s-cTnI remained an independent predictor of 1-year mortality [adjusted odds ratio 1.03 for each increase of 0.1 µg L(-1) , 95% confidence interval (CI) 1.02-1.05, P < 0.001] after adjustment for other risk factors including B-type natriuretic peptide. The net reclassification improvement was 68% (P < 0.001), and absolute integrated discrimination improvement was 0.18 (P < 0.001). The diagnostic accuracy of s-cTnI for the diagnosis of AHF as quantified by the area under the receiver operating characteristic curve was 0.78 (95% CI, 0.75-0.82). CONCLUSIONS: Sensitive cardiac troponin I is a strong predictor of short- and long-term prognosis in AHF that helps to reclassify patients in terms of mortality risk. Detectable levels of s-cTnI, even within the normal range, are independently associated with mortality.

[A leak in the lung: endobronchial one-way valve placement as treatment for a persistent bronchopleural fistula]. / Das Leck in der Lunge: Bronchoskopische Ventilimplantation zur Behandlung einer persistierenden bronchopleuralen Fistel.

Patients with bronchopleural fistula are at an increased risk of morbidity and mortality. Treatment of the air leak includes intrathoracic drainage, antibiotic therapy and closure of the fistula, which conventionally has been performed via surgical means. In patients with limited respiratory capacity, less-invasive alternatives are required. Here we report on a 62-year-old patient with underlying severe COPD, who was admitted with a lung abscess and consecutively developed a persistent bronchopleural fistula. Treatment involved antibiotic therapy and endobronchial one-way valve placement, which resulted in termination of the air leak and full recovery.

Characterizing Social Functioning in School-Age Children with Sensory Processing Abnormalities.

Children with sensory abnormalities (SAs) have a variety of social problems resulting in poorer social functioning than children with typical development (TD). We describe the relationship between SAs and social functioning in school-age children with SAs, children with TD and a clinical comparison sample of children with autism spectrum disorder (ASD). Children with SAs demonstrated impaired social functioning on standardized measures. Children with SAs demonstrated worse social functioning than children with TD and equivalent social functioning to children with ASD. Increased SAs were associated with poorer social functioning across all groups. The results suggest that children with SAs experience clinically significant problems with social functioning and future research is needed to develop interventions to support social functioning in this population.

Interleukin family member ST2 and mortality in acute dyspnoea.

OBJECTIVES: The study objective was to investigate the prognostic utility and patient-specific characteristics of ST2 (suppression of tumorigenicity 2), assessed with a novel sensitive assay. BACKGROUND: Suppression of tumorigenicity 2 signalling has been shown to be associated with death in cardiac and pulmonary diseases. DESIGN/SUBJECTS: In an international multicentre cohort design, we prospectively enrolled 1091 patients presenting with acute dyspnoea to the emergency department (ED). ST2 was measured in a blinded fashion using a novel assay and compared to B-type natriuretic peptide (BNP) and NT-proBNP. The primary end-point was mortality within 30 days and 1 year. The prognostic value of ST2 was evaluated in comparison and in addition to BNP and NT-proBNP. RESULTS: Suppression of tumorigenicity 2 concentrations was higher amongst decedents than among survivors (median 85 vs. 43 U mL⁻¹, P < 0.001) and also higher in patients with impaired left ventricular ejection fraction (LVEF) when compared with preserved LVEF (P < 0.001). In receiver operator characteristics analysis, the area under the curve (AUC) for ST2, BNP and NT-proBNP to predict 30-day and 1-year mortality were 0.76, 0.63 and 0.71, and 0.72, 0.71 and 0.73, respectively. The combinations of ST2 with BNP or NT-proBNP improved prediction of mortality provided by BNP or NT-proBNP alone. After multivariable adjustment, ST2 values above the median (50 U mL⁻¹) significantly predicted 1-year mortality (HR 2.3, P < 0.001). CONCLUSION: In patients presenting to the ED with acute dyspnoea, ST2 is a strong and independent predictor of 30-day and 1-year mortality and might improve risk stratification already provided by BNP or NT-proBNP.