High-sensitivity cardiac troponin T and copeptin assays to improve diagnostic accuracy of exercise stress test in patients with suspected coronary artery disease

Background: The average diagnostic sensitivity of exercise stress tests (ESTs) is lower than that of other non-invasive cardiac stress tests. The aim of the study was to examine whether high-sensitivity cardiac troponin T (hs-cTnT) or copeptin concentrations rise in response to inducible myocardial ischaemia and may improve the diagnostic accuracy of ESTs. Methods and results: An EST was performed stepwise on a bicycle ergometer by 383 consecutive patients with suspected or progression of coronary artery disease (CAD). In addition venous blood samples for measurement of hs-cTnT and copeptin were collected prior to EST, at peak exercise, and 4 h after EST. Coronary angiography was assessed for all patients. Patients with significant CAD (n=224) were more likely to be male and older compared to patients with non-significant CAD (n=169). Positive EST was documented in 125 (55.8%) patients with significant CAD and in 69 (43.4%) patients with non-significant CAD. Copeptin and hs-cTnT concentrations at baseline were higher in patients with significant CAD (copeptin: 10.8 pmol/l (interquartile range (IQR) 8.1–15.6) vs 9.4 pmol/l (IQR 7.1–13.9); p=0.04; hs-cTnT: 3.0 ng/l (IQR <3.0–5.4) vs <3.0 ng/l (IQR <3.0); p=0.006). Hs-cTnT improved sensitivity (61.6% vs 55.8%), specificity (67.7% vs 56.6%) and the positive predictive value (PPV) (72.3% vs 64.4%) and negative (55.2% vs 47.6%) predictive value (NPV) of EST. Copeptin could not improve sensitivity (55.4% vs 55.8%) and reduced specificity, PPV and NPV. Conclusions: The measurement of hs-cTnT during EST improves sensitivity, specificity, and positive and negative predictive values. In contrast, measurement of copeptin does not improve diagnostic sensitivity and reduces specificity

Five‐year follow‐up of patients who underwent everolimus‐eluting bioresorbable scaffold implantation

Objectives The aim of this study was to evaluate very long‐term results after unrestricted everolimus‐eluting bioresorbable scaffolds (BRS) implantation. Background Previous randomized studies mainly included selected patients differing from those seen during daily routine and long‐term data from all‐comers registries are sparse. Methods Consecutive patients undergoing BRS implantation were included in this observational, single center study. Clinical follow‐up was conducted up to 5 years. Endpoint of interest was the composite of target lesion failure (TLF), including target‐vessel myocardial infarction and target lesion revascularization and cardiac death. Furthermore, ARC‐defined scaffold thrombosis (ScT) were assessed. Results A total of 176 patients with a median age of 64 (55 – 72) years were analyzed, of which 59.6% presented an acute coronary syndrome. A total of 183 mainly complex lesions (55.8%) were treated. At 5 years, the rate for TLF was 21.6%. Definite or probable ScT rate was 4.1%. The rate of ScT within the first year was 2.8% and afterwards 1.2%. Notably, no ScT was seen later than 2 years. Conclusions Although this real‐world registry displays high rates of clinical events during long‐term follow‐up, no ScT was seen after 2 years

N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory responses in vitro

El presente trabajo fin de máster presenta una visión de conjunto de la teoría de la fraseología, caracterización y diferentes clasificaciones de unidades fraseológicas, así como la problemática de la equivalencia interlingüística. El trabajo también incluye un análisis contrastivo de unidades fraseológicas con el componente Dios (también en minúscula) en croata y sus equivalentes en el nivel sistémico en español, o al menos funcionales y/o comunicativos si los primeros no existen. El dicho análisis se centra en tres aspectos principales –gramatical, léxico-semántico y pragmático– y también incluye ejemplos de uso de cada UF analizada.Ovaj diplomski rad predstavlja pregled teorije frazeologije, karakterizacije i različite klasifikacije frazema, kao i problematiku međujezične ekvivalencije. Rad uključuje i kontrastivnu analizu frazema koji u sebi sadrže sastavnicu Bog (također pisana i malim slovom) u hrvatskome i njihovim ekvivalentima na sustavnoj razini u španjolskom, ili barem funkcionalnim i/ili komunikacijskim ekvivalentima, ako već ne postoje na razini sustava. Analiza se svodi na tri osnovna aspekta – gramatički, leksičko-semantički i pragmatički – i također uključuje primjere uporabe svakog analiziranog frazema.The present master's thesis presents an overview of the theory of phraseology, characterization and classifications of phraseological units, as well as the problematic of interlinguistic equivalence. The work also includes a contrastive analysis of phraseological units with the component God (also in lower case) in Croatian and their equivalents on the systemic level in Spanish, or at least functional and/or communicative equivalents if the former are non-existent. The analysis is centered on three primary aspects – the grammatical, lexical-semantic and pragmatic – and also includes the examples of usage of each analyzed phraseological unit

In-depth cell-free DNA sequencing reveals genomic landscape of Hodgkin's lymphoma and facilitates ultrasensitive residual disease detection

Background: Individualization of treatment in Hodgkin's lymphoma is necessary to improve cure rates and reduce treatment side effects. Currently, it is hindered by a lack of genomic characterization and sensitive molecular response assessment. Sequencing of cell-free DNA is a powerful strategy to understand the cancer genome and can be used for extremely sensitive disease monitoring. In Hodgkin's lymphoma, a high proportion of cell-free DNA is tumor-derived, whereas traditional tumor biopsies only contain a little tumor-derived DNA. Methods: We comprehensively genotype and assess minimal residual disease in 121 patients with baseline plasma as well as 77 follow-up samples from a subset of patients with our targeted cell-free DNA sequencing platform. Findings: We present an integrated landscape of mutations and copy number variations in Hodgkin's lymphoma. In addition, we perform a deep analysis of mutational processes driving Hodgkin's lymphoma, investigate the clonal structure of Hodgkin's lymphoma, and link several genotypes to Hodgkin's lymphoma phenotypes and outcome. Finally, we show that minimal residual disease assessment by repeat cell-free DNA sequencing, as early as a week after treatment initiation, predicts treatment response and progression-free survival, allowing highly improved treatment guidance and relapse prediction. Conclusions: Our targeted cell-free DNA sequencing platform reveals the genomic landscape of Hodgkin's lymphoma and facilitates ultrasensitive detection of minimal residual disease. Funding: Mildred Scheel School of Oncology Aachen-Bonn-Cologne-Düsseldorf MD Research Stipend, Next Generation Sequencing Competence Network grant 423957469, Deutsche Krebshilfe grant 70112502, Deutsche Forschungsgemeinschaft (DFG) grant EN 179/13-1, the HL MRD consortium, and the Frau-Weiskam und Christel Ruranski-Stiftung