Verbesserte Risikostratifizierung von Patienten mit Verdacht auf ein akutes Koronarsyndrom ohne ST-Streckenhebung durch hochsensitiv gemessenes Troponin T und Copeptin

Das akute Koronarsyndrom (ACS) stellt eine kritische Phase der KHK dar, die mit hoher Morbidität und Mortalität verbunden ist. Anhand des EKGs werden die Patienten in ACS mit ST-Streckenhebung (STEMI) und ohne ST-Streckenhebung (NSTE-ACS) eingeteilt. In letzterer Gruppe unterscheidet man Patienten mit NSTEMI und instabiler Angina (IAP). Hierbei gilt die Troponinbestimmung als Goldstandard bei der Diagnosestellung und Risikostratifizierung. Mit der Einführung hochsensitiver Troponinassays konnte die Identifizierung von Hochrisikopatienten weiter verbessert werden. Allerdings erlauben auch diese immer noch nicht die Erkennung von Patienten mit erst kurz zurückliegendem Brustschmerz und erfordern meist eine sequentielle Testung. Deshalb sind zusätzliche Biomarker wie zum Beispiel das Copeptin von Interesse, um die Diagnostik von Patienten mit Verdacht auf ACS zu verbessern. Copeptin wird als c-terminales Fragment des Arginin-Vasopressin- Prohormons zusammen mit Vasopressin unter akuten Stressbedingungen wie dem AMI von der Neurohypophyse sezerniert. Das Ziel der vorliegenden Arbeit war es, die diagnostische und prognostische Wertigkeit von Copeptin und hochsensitivem c-TnT (hs-cTnT) bei Patienten mit Verdacht auf ein NSTE-ACS zu untersuchen. Bei 321 Patienten mit vermutetem NSTE-ACS wurden hs-cTnT, cTnT und Copeptin zum Aufnahmezeitpunkt bestimmt. Hiervon wurden 137 (42,6%) Patienten aus einer anderen Klinik zugewiesen. Bei 201 (62,6%) Patienten wurde die Diagnose NSTEMI gestellt, 87 (27,1%) hatten eine instabile Angina pectoris und 33 (10,3%) Patienten hatten kein ACS. Die diagnostische Genauigkeit von hs-cTnT zur Diskriminierung von Patienten mit NSTEMI war der von konventionell gemessenem cTnT und Copeptin überlegen. Copeptin bot keinen zusätzlichen Gewinn gegenüber hs-cTnT in der Diagnosestellung des NSTEMI in der vorliegenden Untersuchung („rule in“). Wenn die initiale Troponinkonzentration kleiner der 99. Perzentile gemessen wird und die additive Copeptinbestimmung ebenfalls kleiner der 99. Perzentile ist, so kann allerdings ein AMI mit sehr hoher Wahrscheinlichkeit ausgeschlossen werden („rule out“). In der gegenwärtigen Arbeit war jedoch der Patientenanteil mit einer Troponinkonzentration kleiner der 99. Perzentile im Vergleich zu anderen ACS-Populationen sehr gering. Lediglich 46 Patienten der in der vorliegenden Arbeit untersuchten Patienten hatten eine Troponinkonzentration 14 pmol/L und somit ein erhöhtes Risiko. Die Copeptinkonzentration war im Median bei NSTEMI-Patienten höher als die bei Patienten mit instabiler AP. Allerdings war nur bei 59,2% der NSTEMI-Patienten eine Copeptinkonzentration oberhalb der 99. Perzentile messbar. Patienten, die aus anderen Krankenhäusern zugewiesen wurden, hatten weniger häufig eine erhöhte Copeptinkonzentration. Die Zeit von Symptombeginn bis zur Blutentnahme war bei diesen Patienten länger. Die Cox-Regressionsanalyse veranschaulicht, dass die Copeptinkonzentration direkt von der Zeitverzögerung des Transfers abhängen. Die Zeitverzögerung von Symptombeginn bis zur Blutentnahme muss deshalb in die Interpretation der Copeptinwerte bei Patienten mit Verdacht auf ACS einbezogen werden. Ein diagnostischer Vorteil von Copeptin in der Diagnostik von Patienten mit Verdacht auf ein NSTE-ACS konnte in dieser retrospektiven Analyse nicht gezeigt werden. Jedoch stellt sich Copeptin, neben kardialem Troponin T, als prädiktiver Faktor für die Mortalität innerhalb der ersten 6 Monate und 5 Jahre nach ursprünglicher Hospitalisierung heraus. Die endgültige Bewertung des Stellenwertes von Copeptin in der Diagnostik des ACS wird derzeit in einer multizentrisch-randomisierten Studie untersucht.The acute coronary syndrome (ACS) represents the critical phase of the coronary artery disease, which is associated with high morbidity and mortality. Based on the ECG, patients are subdivided in ACS with ST-Elevation (STEMI) and without ST-Elevation (NSTE-ACS). In the latter group patients with non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) are differentiated. In this setting, troponin (cTnT) measurements are regarded as gold standard for diagnosis finding and risk stratification. The introduction of high-sensitive troponin (hs-cTnT) assays allowed improving identification of high-risk patients. However, in patients presenting early after chest pain onset, sequential testing is still necessary. Accordingly, additional biomarkers like copeptin are of interest to improve early diagnosis and risk stratification of patients with ACS. Copeptin, the c-terminal fragment of the arginine-vasopressin-prohormon, is released under stress conditions, e.g. AMI, from the pituitary gland. The aim of this study was to investigate the diagnostic and prognostic role of copeptin and hs-cTnT in patients presenting with symptoms suggestive of ACS. In 321 patients with suspected NSTE-ACS hs-cTnT, cTnT and copeptin were determined on hospital admission. Out of these, 137 (42,6%) patients were transferred from other hospitals. In total, 201 (62,6%) had the discharge diagnosis of NSTEMI, 87 (27,1%) presented with UA, and in 33 (10,3%) patients ACS could be excluded. The diagnostic accuracy of hs-cTnT for discriminating patients with NSTEMI was superior compared to cTnT and copeptin. Accordingly, the measurement of copeptin alone did not provide any additional benefit in diagnosing NSTEMI compared to hs-cTnT in our cohort („rule in“). This is in contrast to other published data demonstrating that the measurement of copeptin improves early “rule-out” of AMI. When copeptin and troponin values were below the 99.percentile on admission, AMI could reliably be excluded. However, in contrast to published ACS populations the proportion of patients with troponin concentrations below the 99. percentile was very low in our study cohort. Only 46 (14.3%) patients had troponin values <14ng/L, but in 1/3 of these patients with later diagnosed ACS had elevated copeptin levels at presentation. The median copeptin concentration was higher in patients with NSTEMI than in patients with UA. However only 60% of the patients with NSTEMI had elevated copeptin levels. In patients referred from other hospitals copeptin was less frequently elevated, which was linked to longer time delay from symptom onset until first blood sample. Cox-regression analysis confirmed that copeptin concentrations are directly related to time delay of transfer. In conclusion time delay from symptom onset until first blood sample should be considered for the interpretation of copeptin level in general. The improvement in diagnosing ACS by adding copeptin could not be demonstrated in this retrospective analysis. However copeptin proved to carry independent value in predicting mortality 6 month and 5 years after initial hospitalization. The clinical role of copeptin for diagnosing ACS is currently analyzed further in a randomized multicenter trial

Major abdominal surgery in Jehovah’s Witnesses

Introduction Patients who are Jehovah’s Witnesses pose difficult ethical and moral dilemmas for surgeons because of their refusal to receive blood and blood products. This article outlines the personal experiences of six Jehovah’s Witnesses who underwent major abdominal surgery at a single institution and also summarises the literature on the perioperative care of these patients. Methods The patients recorded their thoughts and the dilemmas they faced during their surgical journey. We also reviewed the recent literature on the ethical principles involved in treating such patients and strategies recommended to make surgery safer. Results All patients were supported in their decision making by the clinical team and the Hospital Liaison Committee for Jehovah’s Witnesses. The patients recognised the ethical and moral difficulties experienced by clinicians in this setting. However, they described taking strength from their belief in Jehovah. A multitude of techniques are available to minimise the risk associated with major surgery in Jehovah’s Witness patients, many of which have been adopted to minimise unnecessary use of blood products in general. Nevertheless, the risks of catastrophic haemorrhage and consequent mortality remain an unresolved issue for the treating team. Conclusions Respect for a patient’s autonomy in this setting is the overriding ethical principle, with detailed discussion forming an important part of the preparation of a Jehovah’s Witness for major abdominal surgery. Clinicians must be diligent in the documentation of the patient’s wishes to ensure all members of the team can abide by these

The Presampler for the Forward and Rear Calorimeter in the ZEUS Detector

The ZEUS detector at HERA has been supplemented with a presampler detector in front of the forward and rear calorimeters. It consists of a segmented scintillator array read out with wavelength-shifting fibers. We discuss its desi gn, construction and performance. Test beam data obtained with a prototype presampler and the ZEUS prototype calorimeter demonstrate the main function of this detector, i.e. the correction for the energy lost by an electron interacting in inactive material in front of the calorimeter.Comment: 20 pages including 16 figure

Особенности и закономерности изменения восстановлености углей башкирского яруса Западного Донбасса

В статье приведена детальная петрографическая характеристика углей башкирского яруса Западного Донбасса. Проведена классификация по восстановлености в соответствии с петрографическими типами. Установлены стратиграфические и площадные закономерности изменения степени восстановлености.У статті наведена детальна петрографічна характеристика вугілля башкирського ярусу Західного Донбасу. Проведена класифікація відновленості, згідно з петрографічними типами. Встановлені стратиграфічні та просторові закономірності зміни ступеню відновленості.The article gives detailed petrographic characteristics of coal of Bashkirian formation of Western Donbas. The classifications for recovery in accordance with petrographic types are given. The stratigraphic and areal patterns of change in the degree of recovery are established

Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease

BACKGROUND: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks). RESULTS: In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors' microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25+ Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO. CONCLUSIONS: These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments. Video abstract

The quest for companions to post-common envelope binaries: I. Searching a sample of stars from the CSS and SDSS

As part of an ongoing collaboration between student groups at high schools and professional astronomers, we have searched for the presence of circum-binary planets in a bona-fide unbiased sample of twelve post-common envelope binaries (PCEBs) from the Catalina Sky Survey (CSS) and the Sloan Digital Sky Survey (SDSS). Although the present ephemerides are significantly more accurate than previous ones, we find no clear evidence for orbital period variations between 2005 and 2011 or during the 2011 observing season. The sparse long-term coverage still permits O-C variations with a period of years and an amplitude of tens of seconds, as found in other systems. Our observations provide the basis for future inferences about the frequency with which planet-sized or brown-dwarf companions have either formed in these evolved systems or survived the common envelope (CE) phase.Comment: accepted by A&