The age pattern of suicide in Hungary

Abstract

Taking a cross-national approach, this paper points out some important features of the age pattern of suicide in Hungary. It shows that the rise with age in the risk of suicide is much steeper in Hungary than in a sample of other countries. As a result, the degree to which suicide mortality in Hungary exceeds international levels increases as we move along the age axis. It also shows that, unlike many Western countries, the suicide rate for the young remained fairly stable from 1960 to 1980, whereas that for the elderly rose rather steeply during the same period. On the whole, the results suggest that while young suicide has become a major public health concern in many countries, self-destruction in Hungary is still largely a problem of the older age groups.     

Treatment of coronary bifurcation lesions with drug-eluting stents: insights from the first phase of the prospective multicenter german drug-eluting stent registry

Background: Controversy exists about the impact of treating bifurcations on overall outcome of coronary interventions using drug‐eluting stents (DES). We sought to investigate 1‐year outcome of the treatment of bifurcation lesions using DES in a large “real‐world” cohort. Methods and Results: Among 5,126 patients enrolled in phase I of the multicenter German Drug‐Eluting Stent Registry, 814 (16%) were treated for a bifurcation lesion. Patients with bifurcations were compared to those without bifurcations in terms of baseline characteristics, major adverse cardiac and cerebrovascular events (MACCE) and target vessel revascularization (TVR) at 1 year. Usage of sirolimus‐eluting stents (SES) versus paclitaxel‐eluting stents (PES) was also evaluated. In total, 1,021 and 5,189 stents were implanted in the bifurcation (1.25 stents/patient) and nonbifurcation (1.2 stents/patient) group, respectively, but 64.5% of bifurcation lesions were treated with a single stent. More complex lesion and procedural characteristics were observed in the bifurcation group. However, there was no difference in 1‐year MACCE rates (a composite of death, myocardial infarction, and stroke) between the bifurcation group and nonbifurcation group (8.1% vs. 8.3%, P = 0.85). Rates of TVR (11.2% vs. 10.8%, P = 0.75) and Academic Research Consoritum‐defined definite stent thrombosis (0.9% vs. 0.8%, P = 0.67) were also comparable. MACCE and TVR rates remained similar after adjustment for differences in baseline characteristics. MACCE and TVR in SES patients were 7.2% and 12.6% versus 8.7% and 10.2% in PES patients (P = 0.46 and P = 0.30, respectively). Conclusion: In this large multicenter registry, treatment of bifurcation lesions with DES appears effective and safe. The presence of bifurcations did not affect 1‐year outcomes after DES implantation. The outcomes for SES and PES were similar. (J Interven Cardiol 2012;25:344–352)     

From the Cover: Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery

For many intraoperative decisions surgeons depend on frozen section pathology, a technique developed over 150 y ago. Technical innovations that permit rapid molecular characterization of tissue samples at the time of surgery are needed. Here, using desorption electrospray ionization (DESI) MS, we rapidly detect the tumor metabolite 2-hydroxyglutarate (2-HG) from tissue sections of surgically resected gliomas, under ambient conditions and without complex or time-consuming preparation. With DESI MS, we identify isocitrate dehydrogenase 1-mutant tumors with both high sensitivity and specificity within minutes, immediately providing critical diagnostic, prognostic, and predictive information. Imaging tissue sections with DESI MS shows that the 2-HG signal overlaps with areas of tumor and that 2-HG levels correlate with tumor content, thereby indicating tumor margins. Mapping the 2-HG signal onto 3D MRI reconstructions of tumors allows the integration of molecular and radiologic information for enhanced clinical decision making. We also validate the methodology and its deployment in the operating room: We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite and demonstrate the molecular analysis of surgical tissue during brain surgery. This work indicates that metabolite-imaging MS could transform many aspects of surgical care.The microscopic review of tissue biopsies frequently remains the sole source of intraoperative diagnostic information, and many important surgical decisions such as the extent of tumor resection are based on this information. This approach is time-consuming, requiring nearly 30 min between the moment a tissue is biopsied and the time the pathologist’s interpretation is communicated back to the surgeon. Even after the report of the final pathologic diagnosis is issued days later, a lot of diagnostic, prognostic, and predictive information is left undiscovered and unexamined within the tissue. Tools that provide more immediate feedback to the surgeon and the pathologist and that also rapidly extract detailed molecular information could transform the management of care for cancer patients.MS offers the possibility for the in-depth analysis of the proteins and lipids that comprise tissues (1, 2). We have recently shown that desorption electrospray ionization (DESI) MS is a powerful methodology for characterizing lipids within tumor specimens (3–6). The intensity profile of lipids ionized from within tumors can be used for classifying tumors and for providing valuable prognostic information such as tumor subtype and grade. Because DESI MS is performed in ambient conditions with minimal pretreatment of the samples (7, 8), there is the potential to provide diagnostic information rapidly within the operating room (4, 6, 9). The ability to quickly acquire such valuable diagnostic information from lipids prompted us to determine whether we could use DESI MS to detect additional molecules of diagnostic value within tumors, such as their metabolites.Recently, recurrent mutations have been described in the genes encoding isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) in a number of tumor types including gliomas (10, 11), intrahepatic cholangiocarcinomas (12), acute myelogenous leukemias (13), and chondrosarcomas (14). These mutant enzymes have the novel property of converting isocitrate to 2-hydroxyglutarate (2-HG) (15). This oncometabolite has pleiotropic effects on DNA methylation patterns (16–18), on the activity of prolyl hydroxylases (19), and on cellular differentiation and growth (20–22). Whereas 2-HG is present in vanishingly small amounts in normal tissues, concentrations are extremely high in tumors with mutations in IDH1 and IDH2—several micromoles per gram of tumor have been reported (15). Several groups have reported that 2-HG can be detected by magnetic resonance spectroscopy and imaging, hence providing a noninvasive imaging approach for evaluating patients (23–27). Although such imaging approaches may provide information to plan surgery and to follow the response to chemotherapeutics, applying them to guide decision making during an operation is currently impractical.The ability to detect 2-HG intraoperatively would be particularly useful because infiltrating gliomas such as IDH1 and IDH2 mutant gliomas are difficult to visualize with conventional means, which contributes to the high prevalence of suboptimal surgical resection. Multiple studies suggest that the more residual tumor remains after surgery, the shorter the patient survival for both low- and high-grade gliomas (28–32). Detecting infiltrating glioma cells by microscopic review is challenging on well-prepared H&E-stained permanent sections, and even more so on H&E-stained frozen sections, which frequently harbor processing artifacts. Thus, 2-HG detection could help to define surgical margins, thereby allowing for more complete resection and for longer survival (31, 32). Moreover, directing patients toward appropriate clinical trials for targeted therapeutics (33) would be facilitated by more rapid molecular categorization of tumors.Here, we show that 2-HG can be rapidly detected from glioma samples using DESI MS under ambient conditions, without complex tissue preparation and during surgery, allowing rapid molecular characterization and providing information that is unattainable by standard histopathology techniques. We also present the first implementation, to our knowledge, of MS within an operating room for the molecular characterization of tissue as part of an image-guided therapy program. We cross-validate our findings using standard pathology techniques. Measuring specific metabolites in tumor tissues with precise spatial distribution and under ambient conditions provides a new paradigm for intraoperative surgical decision making, rapid diagnosis, and patient care management.     

Recognition of new citrulline‐containing peptide epitopes by autoantibodies produced in vivo and in vitro by B cells of rheumatoid arthritis patients

Anti‐citrullinated peptide/protein antibodies (ACPAs) are highly sensitive and specific markers of rheumatoid arthritis (RA). Identification of peptide epitopes that may detect different subgroups of RA patients might have diagnostic and prognostic significance. We have investigated citrulline‐ and arginine‐containing peptide pairs derived from filaggrin, collagen or vimentin, and compared this citrulline‐peptide panel with the serological assays conventionally used to detect ACPAs. Furthermore, we studied if the same citrulline‐peptides identify antibody‐secreting cells in in vitro cultures of RA B cells. Recognition of citrulline‐ and arginine‐containing filaggrin, vimentin and collagen peptide epitopes were tested by Multipin ELISA system, by indirect ELISA and by a peptide‐specific microarray. B cells were purified from blood by negative selection; antibody‐producing cells were enumerated by ELISPOT assay. The panel composed of citrulline‐peptide epitopes of filaggrin, collagen and vimentin was recognized by RA sera with a sensitivity and specificity comparable with the currently used tests. Moreover, the combined citrulline‐peptide panel including the new short epitope peptide of filaggrin, fil311‐315, also identified nearly one‐third of RA cases that were negative for antibodies against cyclic citrullinated peptides, mutated citrullinated vimentin or for rheumatoid factor. The results with the peptide‐specific microarray have shown that although most ACPAs recognizing the four citrulline peptides are IgG, some of them specifically recognizing citrulline‐containing filaggrin peptides (fil311–315 and fil306–326) are IgM, and so may be produced either by newly formed activated B cells or by unswitched B memory cells. Furthermore, the citrulline‐peptides of filaggrin and vimentin detect ACPA‐producing cells, and so could also be applied to study the B cells of RA patients.