Non-coronary predictors of elevated high-sensitive cardiac troponin T (hs-cTnT) levels in an unselected emergency patient cohort.

BACKGROUND: Aim of this study was to evaluate the predictors of hs-cTnT in a non-ACS patient cohort admitted to the emergency department. HYPOTHESIS: Atrial fibrillation and hypertension may not always be sufficient for elevation for hs-cTnT. METHODS: We performed a retrospective, single center study encompassing in total 1003 patients. Individuals were retrospectively divided in ACS- and non-ACS patients by two independent investigators reviewing the medical records. In order to identify predictors of hs-cTnT elevation hazard ratios were calculated for age, gender, vital signs, cardiovascular risk factors, LVEF, serum levels of CRP, hemoglobin, and creatinine. Elevation of hs-cTnT was defined by exceeding 14 ng/L (upper reference limit [URL]). RESULTS: About 987 patients were included while 25 patients were excluded because of missing data. 307 patients (31.4%) met the current guideline requirements of diagnosing an ACS, whereas 671 patients (68.6%) were hospitalized with excluded ACS. In the multivariate analysis age, anemia, CRP, creatinine, and reduced systolic left ventricular ejection fraction were independent predictors of elevated troponin T levels in the non-ACS group. However, hypertensive systolic blood pressure, atrial fibrillation and tachycardia were not predictive for Troponin T elevation in non-ACS patients in this multivariate analysis. CONCLUSIONS: In an unselected, non-ACS patient cohort age, chronic renal failure, inflammatory state, and reduced left ventricular systolic function were associated with hs-cTnT levels above the upper reference limit. Rather, often supposed predictors as atrial fibrillation, hypertension, and tachycardia cannot sufficiently explain increased hs-cTnT in our study. Hence, further studies are needed to assess whether isolated hypertension, tachycardia, or atrial fibrillation sufficiently explain elevated hs-cTnT.

Genomic EWS-FLI1 fusion sequences in Ewing sarcoma resemble breakpoint characteristics of immature lymphoid malignancies.

Chromosomal translocations between the EWS gene and members of the ETS gene family are characteristic molecular features of the Ewing sarcoma. The most common translocation t(11;22)(q24;q12) fuses the EWS gene to FLI1, and is present in 85-90% of Ewing sarcomas. In the present study, a specifically designed multiplex long-range PCR assay was applied to amplify genomic EWS-FLI1 fusion sites from as little as 100 ng template DNA. Characterization of the EWS-FLI1 fusion sites of 42 pediatric and young adult Ewing sarcoma patients and seven cell lines revealed a clustering in the 5' region of the EWS-breakpoint cluster region (BCR), in contrast to random distribution of breakpoints in the FLI1-BCR. No association of breakpoints with various recombination-inducing sequence motifs was identified. The occurrence of small deletions and duplications at the genomic junction is characteristic of involvement of the non-homologous end-joining (NHEJ) repair system, similar to findings at chromosomal breakpoints in pediatric leukemia and lymphoma.

Composition of the ANTIGENome of Helicobacter pylori defined by human serum antibodies.

Helicobacter pylori is the most prevalent human pathogen and although, it remains silent in most individuals for lifetime, colonization may develop into severe gastric and duodenal conditions. Rapidly developing resistance to antibiotic treatment urgently calls for the development of effective vaccines. We determined the ANTIGENome of two clinical isolates of H. pylori, KTH-Ca1 and KTH-Du, derived from patients with gastric cancer and duodenal ulcer, respectively. Using disease-relevant human sera from well-characterized donors we identified 124 annotated ORFs and 54 non-annotated peptides as antigens. Through in vitro validation assays we selected the 20 most promising vaccine candidates. Importantly, two candidates represent proteins that were previously shown to provide protection in models of H. pylori infection. One of the most frequently selected and conserved protein, the siderophore-dependent transporter HP1341, was confirmed to show high reactivity with human serum IgGs. These analyses provide the means to identify novel antigens for the selection of vaccine candidates, as well as disease associated biomarkers.

Vaccination with poly-L-arginine as immunostimulant for peptide vaccines: induction of potent and long-lasting T-cell responses against cancer antigens.

Vaccines that induce high numbers of sustained T cell responses are urgently needed for the treatment of numerous diseases including cancer. Antigen-presenting cells (APCs), the most important of which are dendritic cells, orchestrate antigen-dependent T cell responses in that they present antigens to T cells in an appropriate environment. Here we present evidence that after vaccination with a simple mixture of the cationic poly-amino acid poly-L-arginine and tumor antigen-derived peptide antigens, large numbers of antigen-specific T cells are induced and APCs mediate the generation of T lymphocytes. We observe that after s.c. injection, MHC class II(+) cells infiltrate injection sites and are loaded with large amounts of antigen in vivo under the influence of poly-L-arginine. Consequently, numerous antigen-charged APCs can be detected in draining lymph nodes of vaccinated animals. Antigen-specific T cell responses induced are systemic and were readily detected more than 4 months after the last vaccination, the latest time point we measured. By contrast, even after repeat injections, we were consistently unable to detect antibody responses against poly-L-arginine, allowing this compound to be used for numerous booster injections. Clinical trials in cancer patients using poly-L-arginine as immunostimulant will be carried out in the near future.