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OBJECTIVE: The feet of professional dancers are exposed to high work-related stresses. To date, data from the professional dance sector concerning this matter are lacking. The aim of this exploratory project was to analyze and evaluate skin health in the foot area with regard to the prevalence of dermatoses, their locations, as well as gender-specific and load-specific differences. METHODS: Professional classical and neo-classical ballet dancers were examined at two time points: in a phase with increased stress (T0: daily training sessions, rehearsals, and high performance frequency) (n=51, 35 females, 16 males) and after a 24-day rest phase (T1: n=35, 28 females, 7 males). In addition, gender-specific and load-specific (T0 and T1) differences were evaluated. RESULTS: All professional dancers were affected by skin lesions of the feet at T0. Hyperkeratosis (96.1%), onychomycosis (27.5%), and subungual hematoma (11.8%) were the most frequent dermatoses of the feet of professional dancers. Onychomycosis affected the nails of the big toes in particular (right 15.7%; left 13.7%), and subungual hematomas were found exclusively on the nails of the first toe (right 7.8%; left 7.8%). Women tended to be more frequently affected by hyperkeratosis, men more frequently by onychomycosis. There were no load-specific differences between the stress and rest phases. CONCLUSION: The prevalence of work-related dermatoses is equally high among female and male dancers. The results can be used for further research and serve as a basis for specific measures of behavioral and environmental prevention in dance.

In the present study, a deep learning approach based on a long short-term memory (LSTM) neural network is applied for the prediction of transonic wing buffet pressure. In particular, fluctuations in surface pressure over a certain time period as measured by a piezoresistive pressure sensor, are considered. As a test case, the generic XRF-1 aircraft configuration developed by Airbus is used. The XRF-1 configuration has been investigated at different transonic buffet conditions in the European Transonic Wind tunnel (ETW). During the ETW test campaign, sensor data has been obtained at different local span—and chordwise positions on the lower and upper surface of the wing and the horizontal tail plane. For the training of the neural network, a buffet flow condition with a fixed angle of attack $$\alpha$$ α and a fixed sensor position on the upper wing surface is considered. Subsequent, the trained network is applied towards different angles of attack and sensor positions considering the flow condition applied for training the network. As a final step, the trained LSTM neural network is used for the prediction of pressure data at a flow condition different from the flow condition considered for training. By comparing the results of the wind tunnel experiment with the results obtained by the neural network, a good agreement is indicated.

Funding Acknowledgements Type of funding sources: None. Introduction According to current guidelines, primary prophylactic ICD implantation is indicated with a class IA recommendation in patients with severely reduced EF < 35% and ischaemic heart disease. However, it is unclear whether there are differences in patient outcomes related to the localization of myocardial infarction. Aim of the study was to compare the incidence of ventricular tachyarrhythmias and clinical outcomes in primary prophylactic ICD-patients with ischaemic heart disease in relation to the localization of myocardial infarction. Methods A total of 448 consecutive ICD patients from a prospective single-centre ICD-registry who underwent primary prophylactic ICD implantation due to ischaemic cardiomyopathy between 1996 and 2021 were analyzed. Patients with previous anterior wall myocardial infarction (AWMI, n = 293) were compared to those with posterior wall myocardial infarction (PWMI, n = 155). Patients with both AWMI and PWMI were excluded. The median follow-up time was 6 years in both groups. Results Patients with AMWI were younger, more often female, and less often received cardiac synchronization therapy (Table 1). Patients with previous PWMI more often had ICD therapy during follow-up (Figure 1) due to the higher incidence of ventricular tachycardias (Table 1). The all-cause mortality rate was similar between both groups. Conclusion Primary prophylactic ICD patients with previous PWMI have a 10% higher incidence of ventricular tachycardias after 6-year follow-up than ICD patients with previous AMWI. This might be explained by the proximity of the inferior infarction to the mitral isthmus and should be considered when ablating VTs in patients with PWMI.

Background: Andexanet alfa is a modified recombinant inactive factor Xa (FXa) designed to reverse FXa inhibitors. ANNEXA-4 (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) was a multicenter, prospective, phase-3b/4, single-group cohort study that evaluated andexanet alfa in patients with acute major bleeding. The results of the final analyses are presented. Methods: Patients with acute major bleeding within 18 hours of FXa inhibitor administration were enrolled. Co-primary end points were anti-FXa activity change from baseline during andexanet alfa treatment and excellent or good hemostatic efficacy, defined by a scale used in previous reversal studies, at 12 hours. The efficacy population included patients with baseline anti-FXa activity levels above predefined thresholds (≥75 ng/mL for apixaban and rivaroxaban, ≥40 ng/mL for edoxaban, and ≥0.25 IU/mL for enoxaparin; reported in the same units used for calibrators) who were adjudicated as meeting major bleeding criteria (modified International Society on Thrombosis and Haemostasis definition). The safety population included all patients. Major bleeding criteria, hemostatic efficacy, thrombotic events (stratified by occurring before or after restart of either prophylactic [ie, a lower dose, for prevention rather than treatment] or full-dose oral anticoagulation), and deaths were assessed by an independent adjudication committee. Median endogenous thrombin potential at baseline and across the follow-up period was a secondary outcome. Results: There were 479 patients enrolled (mean age, 78 years; 54% male; 86% White); 81% were anticoagulated for atrial fibrillation, and the median time was 11.4 hours since last dose, with 245 (51%) on apixaban, 176 (37%) on rivaroxaban, 36 (8%) on edoxaban, and 22 (5%) on enoxaparin. Bleeding was predominantly intracranial (n=331 [69%]) or gastrointestinal (n=109 [23%]). In evaluable apixaban patients (n=172), median anti-FXa activity decreased from 146.9 ng/mL to 10.0 ng/mL (reduction, 93% [95% CI, 94–93]); in rivaroxaban patients (n=132), it decreased from 214.6 ng/mL to 10.8 ng/mL (94% [95% CI, 95–93]); in edoxaban patients (n=28), it decreased from 121.1 ng/mL to 24.4 ng/mL (71% [95% CI, 82–65); and in enoxaparin patients (n=17), it decreased from 0.48 IU/mL to 0.11 IU/mL (75% [95% CI, 79–67]). Excellent or good hemostasis occurred in 274 of 342 evaluable patients (80% [95% CI, 75–84]). In the safety population, thrombotic events occurred in 50 (10%) patients; in 16 patients, these occurred during treatment with prophylactic anticoagulation that began after the bleeding event. No thrombotic episodes occurred after oral anticoagulation restart. Specific to certain populations, reduction of anti-FXa activity from baseline to nadir significantly predicted hemostatic efficacy in patients with intracranial hemorrhage (area under the receiver operating characteristic curve, 0.62 [95% CI, 0.54–0.70]) and correlated with lower mortality in patients P =0.022; unadjusted P =0.003). Median endogenous thrombin potential was within the normal range by the end of andexanet alfa bolus through 24 hours for all FXa inhibitors. Conclusions: In patients with major bleeding associated with the use of FXa inhibitors, treatment with andexanet alfa reduced anti-FXa activity and was associated with good or excellent hemostatic efficacy in 80% of patients. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02329327.

In the present study, a hybrid deep learning reduced-order model (ROM) is applied for the prediction of wing buffet pressure distributions on a civil aircraft configuration. The hybrid model is compound of a convolutional variational neural network autoencoder (CNN-VAR-AE) and a long short-term memory (LSTM) neural network. The CNN-VAR-AE is used for the reduction of the high-dimensional flow field data, whereas the LSTM is applied to predict the temporal evolution of the pressure distributions. For training the neural network, experimental buffet data obtained by unsteady pressure sensitive paint measurement (iPSP), is applied. As a test case, the Airbus XRF-1 configuration is selected, considering two different experimental setups. The first setup is defined by a wind tunnel model with a clean wing, whereas the second setup includes an ultra high bypass ratio engine nacelle on each wing. Both configurations have been tested in the European Transonic Windtunnel, considering several transonic buffet conditions. Finalizing the training of the hybrid neural networks, the trained models are applied for the prediction of buffet flow conditions which are not included in the training data set. A comparison of the experimental results and the pressure distributions predicted by the hybrid ROMs indicate a precise prediction performance. Considering both aircraft configurations, the main buffet flow features are captured by the hybrid ROMs.

In the present study, a nonlinear system identification approach based on a long short-term memory (LSTM) neural network is applied for the prediction of transonic buffet aerodynamics. The identification approach is applied as a reduced-order modeling (ROM) technique for an efficient computation of time-varying integral quantities such as aerodynamic force and moment coefficients. Therefore, the nonlinear identification procedure as well as the generalization of the ROM are presented. The training data set for the LSTM–ROM is provided by performing forced-motion unsteady Reynolds-averaged Navier–Stokes simulations. Subsequent to the training process, the ROM is applied for the computation of the aerodynamic integral quantities associated with transonic buffet. The performance of the trained ROM is demonstrated by computing the aerodynamic loads of the NACA0012 airfoil investigated at transonic freestream conditions. In contrast to previous studies considering only a pitching excitation, both the pitch and plunge degrees of freedom of the airfoil are individually and simultaneously excited by means of an user-defined training signal. Therefore, strong nonlinear effects are considered for the training of the ROM. By comparing the results with a full-order computational fluid dynamics solution, a good prediction capability of the presented ROM method is indicated. However, compared to the results of previous studies including only the airfoil pitching excitation, a slightly reduced prediction performance is shown.

Background The role of triggers in the occurrence of appropriate ICD shocks due to ventricular tachyarrhythmias is not well known. The aim of the study was to assess the prevalence of trigger factors in appropriate ICD shocks and to analyze their prognostic impact on clinical outcome. Methods A total of 710 consecutive patients of a prospective single-centre ICD-registry who received a first appropriate ICD shock between 2000 and 9/2021 were analyzed. Results In 35% of ICD patients with first ICD shock, at least one of the following triggers was found: Ischemia (22%), Compliance (9%), Decompensation (38%), Stress (12%), Technical (5%), Electrolyte/endocrinological disorder (22%) and Medication intoxication (4%) (Table 1). The trigger factors can be summarized under the acronym ICD-STEMi. Patients with trigger associated ICD shocks had a more depressed ejection fraction and presented more often with ventricular fibrillation or electrical storm. The therapy after VT/VF shock in the trigger group comprised trigger optimization in 100% and heart failure optimization in 21% as compared to 0% respectively 10% in the no-trigger group (p Conclusions In one third of ICD patients with first appropriate ICD shock, at least one trigger can be identified. Finding a trigger strongly influenced therapy after VT/VF shock. Patients with triggered ICD shock have a higher 5-year mortality rate. The evaluation of trigger factors after the occurrence of ICD shocks is mandatory and can be systematically evaluated using the acronym ICD-STEMi. Funding Acknowledgement Type of funding sources: None.

Background Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor has become standard of care for patients with NSTE-ACS. Guidelines recommend prasugrel and ticagrelor over clopidogrel. In the ISAR-5 trial prasugrel was superior to ticagrelor in NSTE-ACS patients. We evaluated the outcome of patients undergoing PCI for NSTE-ACS in a large number of patients in real life and compared patients treated with prasugrel and ticagrelor. Methods We used the data of the prospective German ALKK-PCI registry and included patients treated with prasugrel or ticagrelor and undergoing PCI for NSTE-ACS treated in 42 centers. Baseline variables, procedural features, antithrombotic therapies and in-hospital outcomes were centrally collected and analysed. Patients with cardiogenic shock were excluded. Results Between 2011 and 2020 a total of 7888 patients Conclusion In clinical practice in patients with NSTE-ACS undergoing PCI ticagrelor was used more often than prasugrel. Ticagrelor treated patients were older and had more comorbidities. Despite this higher risk profile in ticagrelor patients the in-hospital mortality and the short-term safety profile were comparable in both groups. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Institut für Herzinfarktforschung Ludwigshafen

According to the social domains hypothesis, we reduce the information-processing demands of\ud complex social cues by classifying them into a limited number of domains, each with distinct sets\ud of expectations. This requires rapid identification of violations of the boundaries between\ud domains. We hypothesised that these violations are likely to be associated with neural activation\ud of the salience system. Using fMRI we compared responses of 20 adults to expected and\ud unexpected everyday social scenarios in personal and work interactions. The vignettes\ud exemplified different kinds of scenarios presented in the work setting, i.e., task-focused scenarios\ud which are expected at work and scenarios with a personal focus which are unexpected at work.\ud The key contrast between task and personal focussed scenarios presented in the work setting\ud was associated with fronto-insular activation. Perceived inappropriateness of the unexpected\ud scenarios, and shorter response time to judgement of inappropriateness, were also associated\ud with fronto-insular activation, after controlling for unpleasantness. This study indicates specific\ud neural responses to violations of expectations in different social situations. Our findings suggest\ud that the fronto-insular region is implicated in rapid detection of behaviours that cross the\ud boundaries of social domains which are hypothesised to be necessary for efficient social\ud information processing.

Background Interventional closure of symptomatic paravalvular leaks (PVL) after surgical or interventional valve replacement by plug implantation has emerged as an alternative to surgical correction, which is associated with high morbitity and mortality rates. To date, data on procedural efficacy and clinical outcome after transcatheter closure with plugs is sparse, especially prospective data are missing. Methods We analysed data from a multi-center prospective registry on interventional PVL closure with plug devices. Results Between 06/2012 and 04/2020 55 interventions were performed with different numbers of plugs (maximal 4) in 51 patients at 9 hospitals. Interventions were performed in 15 women and 36 men at high surgical risk for repeat surgery. 48% of procedures were performed for mitral PVLs and 52% procedures were performed for aortic PVLs. Mean age of the population treated was 69±13 years and mean log. Euro-Score I was 22.5±14.2%. Patients were treated by implantation of Amplatzer Vascular Plug III (80%) and Occlutec occluders (9%). Aortic PVLs were treated using a retrograde transfemoral access, mitral PVLs were treated using either a transseptal (25/26) or transapical access (1/26) with 3-dimensional transesophageal echocardiographic and fluoroscopic guidance. Indication for PVL closure was previous surgery (n=39), high-risk patients (n=24), heart failure (n=22), age (n=20) and hemolysis (n=12). 40 patients had NYHA class III/IV at admission. Interventional closure of PVL was completely successful in 40 procedures (73%), partially successful in 7 procedures (13%) and failed in 7 procedures (13%). NYHA class I/II after PVL closure was achieved in 75% patients. However, 8 out of 12 patients with hemolysis as indication still hemolyzed at discharge. Complications occurred in 16% of patients. In-hospital mortality rate was 4% of procedures (2/51). After hospital discharge no death occurred during 30-day follow-up. Conclusions In this prospective interventional PVL registry inclusion rate was lower than expected. There was an equal distribution of aortal and mitral PVLs. At least partial success could be achieved in 86% of patients, with significant functional improvement in most patients. In this high risk population hospital mortaliy was low (4%), indicating that interventional PVL treatment should be the treatment of choice, when discussed by a heart team. Funding Acknowledgement Type of funding sources: None.

Im professionellen Tanz wird insbesondere die Achillessehne im Bereich des Sprunggelenks mechanisch stark belastet. Die charakteristischen Bewegungselemente begunstigen die Entstehung von Fehl- oder Uberlastungsschaden der Achillessehne. Chronische Erkrankungen der Achillessehne stellen eine Gefahrdung der Berufsausubung als Tanzer/in dar und sollten im Rahmen von arbeitsbezogenen Praventionsmasnahmen vermieden werden. Diese Ubersicht thematisiert den bisherigen Forschungsstand.

A 59-year-old male patient was admitted to hospital diagnosed with moderate pneumonia associated with COVID-19. Upfront treatment with hydroxychloroquine and azithromycin was started. Due to a clinical deterioration (ARDS, circulatory shock) and greatly increased inflammation markers 6 days after admission, a cytokine storm was suspected and off-label treatment with the IL‑6 receptor antagonist tocilizumab was initiated. Subsequently there was a dramatic rise of D‑dimers indicating pulmonary intravascular coagulopathy and respiratory insufficiency worsened. After a second dose of tocilizumab was administered severe perimyocarditis with cardiac arrhythmia, hemodynamic instability and ST elevation occurred. Shortly afterwards the patient died due to multiorgan failure. From our experience, exacerbation of COVID-19 following treatment with tocilizumab cannot be ruled out. Randomized controlled studies are necessary to further investigate the efficacy, safety and patient selection criteria for tocilizumab treatment in COVID-19.Ein 59-jähriger Patient wurde wegen einer COVID-19-assoziierten Pneumonie stationär in einem Krankenhaus der Maximalversorgung mit Hydroxychloroquin und Azithromycin behandelt. Aufgrund einer klinischen Verschlechterung (ARDS, Kreislaufschock) sowie stark erhöhten Inflammationsmarkern 6 Tage nach Aufnahme wurde ein Zytokinsturm vermutet und daher der IL-6-Rezeptor-Blocker Tocilizumab verabreicht, woraufhin es zu einer Gerinnungsaktivierung und zunehmender respiratorischer Insuffizienz kam. Direkt nach Zweitgabe des Medikaments am Folgetag trat eine Perimyokarditis mit schweren Herzrhythmusstörungen auf. Der Patient verstarb kurz danach im Multiorganversagen. Eine Verschlechterung des Krankheitsbildes durch Tocilizumab ist unserer Erfahrung nach nicht auszuschließen.

Type B aortic dissection is a relatively rare clinical picture that involves many fields of medicine and requires a multidisciplinary approach. In this report, the disciplines involved constitute the most important aspects of the new S2k guidelines for the diagnosis and treatment of type B aortic dissection. More specifically, the definition and epidemiology, the clinical and technical diagnostic methods, in addition to the imaging methods, are presented, and recommendations for the individual topics based on scientific studies and expert opinion are given. In the guidelines, the various procedures related to the main conservative and surgical treatment regimes in the acute, subacute, and chronic phases of the condition are dealt with.

Die Typ-B-Aortendissektion ist ein relativ seltenes Krankheitsbild, welches in sehr vielen Bereichen der Medizin vorkommt und einen interdisziplinaren Behandlungsansatz erfordert. Die beteiligten Disziplinen stellen in diesem Beitrag die wesentlichen Aspekte der neuen S2k-Leitlinie zur Diagnostik und Therapie der Aortendissektion Typ B dar. Im Einzelnen werden die Definition und Epidemiologie, die klinische und instrumentelle Diagnostik sowie die bildgebenden Verfahren dargestellt und zu den einzelnen Themen aufgrund von wissenschaftlichen Studien und Expertenmeinung Empfehlungen gegeben. In der Leitlinie wird auserdem auf die unterschiedlichen Vorgehensweisen in Bezug auf primar konservative und operative Therapieregime in der akuten, subakuten und chronischen Phase der Erkrankung eingegangen.

Die 2017 veroffentlichte „European Society of Cardiology“(ESC)-Leitlinie „Periphere Arterielle Erkrankungen“ (PAE, „peripheral arterial diseases“) umfasst Empfehlungen zur Diagnostik und Therapie von atherosklerotischen Manifestationen in peripheren Gefasen. Es werden zu allen arteriellen Versorgungsgebieten mit Ausnahme der Aorta und Koronararterien Empfehlungen formuliert. Der folgende Kommentar bezieht sich auf die Ubersetzung der Pocket-Leitlinie und ist fokussiert auf die Empfehlungen zur Sekundarpravention, zur peripheren arteriellen Verschlusskrankheit (pAVK) und zur Karotisstenose. In den Empfehlungen zur Sekundarpravention wird die Atherosklerose als Erkrankung des gesamten Gefassystems betrachtet. Generell wird eine konsequente Einstellung der kardiovaskularen Risikofaktoren mit absoluter Rauchkarenz, dem Einsatz von Statinen sowie einer Blutdruck- und Blutzuckerkontrolle empfohlen. Patienten mit Claudicatio intermittens sollten moglichst ein supervidiertes Gehtraining betreiben. Ein Thrombozytenaggregationshemmer sollte gegeben werden, wenn eine symptomatische pAVK vorliegt oder bei weiteren Manifestationen der Atherosklerose wie beispielsweise einer koronaren Herzerkrankung (KHK). Liegt eine starke Einschrankung im Alltag vor, wird eine Revaskularisation empfohlen. Bei Vorliegen einer Indikation zur Revaskularisation sollte bei kurzen Gefasverschlussen (z. B.

The clinical significance of timely re-epithelialization is obvious in burn care, since delayed wound closure is enhancing the risk of wound site infection and extensive scarring. Topical treatments that accelerate wound healing are urgently needed to reduce these sequelae. Evidence from preliminary studies suggests that betulin can accelerate the healing of different types of wounds, including second degree burns and split-thickness skin graft wounds. The goal of this combined study program consisting of two randomized phase III clinical trials in parallel is to evaluate whether a topical betulin gel (TBG) is accelerating re-epithelialization of split-thickness skin graft (STSG) donor site wounds compared to standard of care. Two parallel blindly evaluated, randomised, controlled, multicentre phase III clinical trials were performed in adults undergoing STSG surgery (EudraCT nos. 2012-003390-26 and 2012-000777-23). Donor site wounds were split into two equal halves and randomized 1:1 to standard of care (a non-adhesive moist wound dressing) or standard of care plus TBG consisting of 10% birch bark extract and 90% sunflower oil (Episalvan, Birken AG, Niefern-Oeschelbronn, Germany). The primary efficacy assessment was the intra-individual difference in time to wound closure assessed from digital photographs by three blinded experts. A total of 219 patients were included and treated in the two trials. Wounds closed faster with TBG than without it (15.3 vs. 16.5 days; mean intra-individual difference=-1.1 days [95% CI, -1.5 to -0.7]; p

Aims The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.

Supplemental Material for Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2 by T Reiff, HH Eckstein, U Mansmann, O Jansen, G Fraedrich, H Mudra, D Böckler, M Böhm, H Brückmann, ES Debus, J Fiehler, W Lang, K Mathias, EB Ringelstein, J Schmidli, R Stingele, R Zahn, T Zeller, A Hetzel, U Bodechtel, A Binder, J Glahn, W Hacke and PA Ringleb in International Journal of Stroke

Bis zu 50 % der hamodynamisch stabilen Patienten mit akutem ST-Strecken-Hebungs-Myokardinfarkt (STEMI) und 70–80 % der Patienten mit infarktbedingtem kardiogenen Schock haben eine koronare Mehrgefaserkrankung. Die optimale Revaskularisationsstrategie bei diesen Patienten ist bislang nicht klar definiert. Nach erfolgreicher perkutaner koronarer Intervention (PCI) der den akuten Infarkt auslosenden Lasion („culprit lesion“) kann eine sofortige Mehrgefas-PCI aller signifikanten Stenosen erfolgen oder aber ein zweizeitiges Vorgehen, ggf. nach Ischamiediagnostik, gewahlt bzw. eine rein konservative Therapie erwogen werden. Die Studien zur sofortigen Mehrgefas-PCI beim STEMI ohne Schock zeigen, dass eine sofortige Mehrgefas-PCI sicher durchgefuhrt werden kann und gegenuber einer streng konservativen Therapie mit einem klinischen Vorteil assoziiert ist. Einen randomisierten Vergleich einer sofortigen mit einer zweizeitigen PCI gibt es bislang nicht. Die Datenlage zum kardiogenen Schock ist auch wegen des Fehlens randomisierter Studien weniger einheitlich. Hier wird die laufende CULPRIT-Shock-Studie naheren Aufschluss uber die zu bevorzugende Strategie geben. Dieser Beitrag fasst die derzeitige Datenlage zusammen und gibt Empfehlungen fur die klinische Routine.

Hypercholesterolemia is one of the major modifiable risk factors for the development of atherosclerosis. Increasing LDL cholesterol is associated with an increased risk of developing cardiovascular diseases as well as cardiovascular ischemic complications. Studies with statins and ultimately with ezetimibe have been able to impressively demonstrate that lowering LDL cholesterol contributes to a significant reduction of cardiovascular ischemic complications.Based on the results of randomized trials for lipid lowering, the practice guidelines developed by the professional societies have defined LDL cholesterol goals. High-risk patients, such as patients with clinically manifest cardiovascular disease, type 2 diabetes, type 1 diabetes with organ damage, moderate or severe chronic kidney disease or a risk of SCORE ≥10 %, should reach LDL cholesterol values

Die akute Herzinsuffizienz (aHF) ist ein lebensbedrohliches Krankheitsbild. Im Gegensatz zur chronischen Herzinsuffizienz ist jedoch die Therapie der aHF deutlich weniger gut untersucht. Wichtig ist zunachst eine rasche Diagnostik, begleitet von einer symptomatischen Therapie. Beim kardiogenen Schock, der extremsten Form der aHF, gilt das Gleiche. Neben der Therapie mit Katecholaminen gibt es hier auch die Moglichkeit des Einsatzes von Kreislaufunterstutzungssystemen, die eine hohe Expertise erfordern und deren Stellenwert wissenschaftlich noch nicht ausreichend gesichert ist. Hier ist die fruhe Verlegung an ein Zentrum, das diese Moglichkeiten vorhalt, immer zu erwagen.

Background Because of recent advances in best medical treatment (BMT), it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit, in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses. The aim was to compare the stroke-preventive effects of BMT alone, with that of BMT in combination with carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with high grade asymptomatic extracranial carotid artery stenosis. Methods SPACE-2 was planned as a three-armed, randomized controlled trial (BMT alone vs. CEA plus BMT vs. CAS plus BMT, ISRCTN 78592017). However, because of slow patient recruitment, the three-arm study design was amended (July 2013) to become two parallel randomized studies (BMT alone vs. CEA plus BMT, and BMT alone vs. CAS plus BMT). Results The change in study design did not lead to any significant increase in patient recruitment, and trial recruitment ceased after recruiting 513 patients over a 5 year period (CEA vs. BMT ( n = 203); CAS vs. BMT ( n = 197), and BMT alone ( n = 113)). The 30 day rate of death/stroke was 1.97% for patients undergoing CEA, and 2.54% for patients undergoing CAS. No strokes or deaths occurred in the first 30 days after randomization in patients randomized to BMT. There were several potential reasons for the low recruitment rates into SPACE-2, including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial, an inability to convince patients (who had come "mentally prepared" that an intervention was necessary) to accept BMT, and other economic constraints. Conclusions Because of slow recruitment rates, SPACE-2 had to be stopped after randomizing only 513 patients. The German Research Foundation will provide continued funding to enable follow up of all recruited patients, and it is also planned to include these data in any future meta-analysis prepared by the Carotid Stenosis Trialists Collaboration.

The number of cardiac pacemaker wearers is continuously increasing in Germany as well as worldwide. The probability of indications for a magnetic resonance imaging (MRI) examination during the lifetime is approximately 50-75% for every person. An MRI examination is nowadays possible for pacemaker wearers under certain conditions. Due to the technical developments during the last 10 years certain MRI-conditional pacemakers are available. The recommendations of the German and American medical specialist societies currently allow an MRI examination in patients with conventional pacemakers beyond the approval conditions (off-label use) under prespecified conditions, based on the study data. This article summarizes the information on conditions of use and reprogramming strategies as well as on the study situation for the clinical routine.

Atrial fibrillation (AF) is the most common form of cardiac tachyarrhythmia. It is estimated that in the Rhein-Neckar region approximately 40,000-50,000 out of 2 million people are affected. Due to demographic changes in the near future there will be a significant increase in the prevalence of AF within the next decades. The ARENA project was initiated by the Foundation Institute for Cardiac Infarction Research (IHF) Ludwigshafen in cooperation with cardiological and neurological departments of neighboring hospitals, resident doctors and pharmacies to improve the awareness and care of patients with AF. The particular aim is the prevention of stroke as one of the most dreaded complications. The project focusses on the following three subtopics: interventions, medication, migration. The aim of the intervention project is to raise awareness of AF as a risk factor for stroke and to improve the diagnostic work-up and care for patients with diagnosed or unknown AF. The subproject medication focusses on the adherence of patients with AF to the prescribed antithrombotic medication. To evaluate differences concerning patients with and without a migration background the subproject migration was initiated.

Acceleration of wound healing promises advantages for patients and caregivers in reducing the burden of disease, avoiding complications such as wound infections, and improving the long-term outcome. However, medicines that can accelerate wound healing are lacking. The objective of this open, blindly evaluated, randomized, multicenter phase III study was to compare intra-individually the efficacy and tolerability of Oleogel-S10 with fatty gauze dressing versus OctenilinAcute superficial partial thickness burn wounds in adults caused by fire, heat burn or scalding were divided into 2 halves and randomly assigned to treatment with Oleogel-S10 or OctenilinOf 61 patients that were enrolled, 57 received the allocated intervention and 48 completed treatment. The percentage of patients with earlier wound healing was significantly higher for Oleogel-S10 (85.7%, n=30) compared to OctenilinOleogel-S10 (Episalvan) significantly accelerated the healing of superficial partial thickness burn wounds. It was safe and well tolerated.

In the extracellular space, the gonadotropin-releasing hormone (GnRH) is metabolized by the zinc metalloendopeptidase EC3.4.24.15 (EP24.15) to form the pentapeptide, GnRH-(1-5). GnRH-(1-5) diverges in function and mechanism of action from GnRH in the brain and periphery. GnRH-(1-5) acts on the orphan G protein-coupled receptor 101 (GPR101) to sequentially stimulate epidermal growth factor (EGF) release, phosphorylate the EGF receptor (EGFR), and facilitate cellular migration. These GnRH-(1-5) actions are dependent on matrix metallopeptidase (MMP) activity. Here, we demonstrated that these GnRH-(1-5) effects are dependent on increased MMP-9 enzymatic activity in the Ishikawa and ECC-1 cell lines. Furthermore, the effects of GnRH-(1-5) mediated by GPR101 and the subsequent increase in MMP-9 enzymatic activity lead to an increase in cellular invasion. These results suggest that GnRH-(1-5) and GPR101 regulation of MMP-9 may have physiological relevance in the metastatic potential of endometrial cancer cells.

Die Gruppe der Patienten mit stabiler chronischer koronarer Herzerkrankung (SCAD) ist sehr inhomogen und umfasst sowohl Patienten mit stabiler Angina pectoris mit vermuteter koronarer Herzerkrankung (KHK) als auch Patienten mit bekannter KHK nach z. B. einem akuten Koronarsyndrom oder nach Koronarintervention, die mittlerweile asymptomatisch sind. Patienten mit SCAD haben ein erhohtes Risiko fur ischamische Komplikationen und profitieren neben der Therapie mit Statinen zur Senkung des LDL-Cholesterins insbesondere von der antithrombozytaren Therapie zur Pravention ischamischer Ereignisse. Patienten mit SCAD bedurfen daher einer lebenslangen antithrombozytaren Therapie mit Azetylsalizylsaure (ASS) 100 mg taglich. Bei ASS-Unvertraglichkeit kann alternativ Clopidogrel 75 mg taglich als Dauertherapie verabreicht werden. Da die chronische KHK in ihrem Verlauf unterschiedliche Auspragungen, von stabilen Phasen bis hin zu einem akuten Koronarsyndrom, annehmen kann, muss die antithrombozytare Therapie fortlaufend uberpruft und den aktuellen Umstanden angepasst werden. Gleiches gilt fur die zusatzliche Indikation fur eine Antikoagulationstherapie wie z. B. Vorhofflimmern. Die vorliegende Arbeit beschrankt sich auf die Beschreibung der langfristigen antithrombozytaren Therapie der stabilen chronischen KHK sowie deren Anpassung bei elektiven perkutanen koronaren Interventionen (PCI).

Bei Patienten mit akutem Koronarysyndrom und Stentimplantation empfehlen die Leitlinien eine duale Thrombozytenhemmung vorzugsweise mit Prasugrel oder Ticagrelor uber die Dauer von 12 Monaten. Probleme ergeben sich bei Patienten mit der Notwendigkeit einer oralen Antikoagulation, wie bei der haufigsten Indikation, dem Vorhofflimmern. Die Kombinationstherapie von oraler Antikoagulation und dualer Thrombozytenhemmung (Triple-Therapie) ist mit einem erhohten Risiko fur Blutungskomplikationen verbunden. Es gibt eine kleinere randomisierte Studie zur antithrombotischen Therapie bei diesen Patienten, die eine niedrigere Rate von Blutungen mit einer Kombination eines Vitamin-K-Antagonisten (VKA) und Clopidogrel im Vergleich zur Triple-Therapie gezeigt hat. Diese Befunde konnten in Registerdaten bestatigt werden. Die neuen oralen Antikoagulanzien haben konsistent zur Reduktion der Rate intrazerebraler Blutungen im Vergleich zu VKA bei Patienten mit Vorhofflimmern auch in Kombination mit Thrombozytenhemmern gefuhrt. Randomisierte Studien zum Einsatz dieser Substanzen nach Stentimplantation im Vergleich zu VKA liegen bislang allerdings nicht vor. Die Entscheidung uber Intensitat und Dauer der Kombination von oraler Antikoagulation und Thrombozytenhemmung sollte daher individuell nach Stentthrombose- und Blutungsrisiko bei dem jeweiligen Patienten getroffen werden. In vielen Fallen scheint zusatzlich zur oralen Antikoagulation nur uber 3 bis 6 Monate eine antithrombozytare Therapie vorzugsweise mit Clopidogrel notwendig.

Loss of heterozygosity (LOH) is a common event in malignant cells. In this work we introduce a new approach to identify patients with loss of heterozygosity in the HLA region either at first diagnosis or after HLA mismatched allogeneic HSCT. Diagnosis of LOH requires a high purity of recipient target cells. FACS is time consuming and also frequently prevented by rather nonspecific or unknown immune phenotype. The approach for recipient cell enrichment is based on HLA targeted complement-dependent cytotoxicity (CDC). Relative fluorescent quantification (RFQ) analysis of HLA intron length polymorphisms then allows analysis of HLA heterozygosity. The approach is exemplified in recent clinical cases illustrating the detection of an acquired allele loss. As illustrated in one case with DPB1, distinct HLA loci in donor and patient were sufficient for both proof of donor cell removal and evaluation of allele loss in the patient's leukemic cells. Results were confirmed using HLA-B RFQ analysis and leukemia-associated aberrant immunophenotype (LAIP) based cell sort. Both results confirmed suspected loss of HLA heterozygosity. Our approach complements or substitutes for FACS-based cell enrichment; hence it may be further developed as novel routine diagnostic tool. This allows rapid recipient cell purification and testing for loss of HLA heterozygosity before and after allogeneic HSCT in easily accessible peripheral blood samples.

Clinical registries have become increasingly more important tools for scientists as well as for medical admission boards worldwide during recent years due to the ability to investigate the safety and efficacy of a therapeutic method in the general population under real world conditions. The clinical benefit of current registry data seems to be particularly high in a treatment method, such as carotid artery stenting (CAS) where safety and efficacy, especially in daily clinical practice, could not be totally clarified by several randomized clinical trials (RCT). For this reason the new multidisciplinary, multicenter and prospective German Carotid Artery Registry (GeCAS) was founded in January 2011 for continuing quality control in CAS in clinical practice in Germany. The GeCAS registry is a fusion of two large German CAS registries, the ALKK-CAS registry and the PROCAS registry, which were conducted by cardiologists, angiologists and radiologists and operated from 1996 until December 2010. However, a general duty of documentation (BQS) of every CAS procedure exists throughout Germany since January 2012. In contrast to optional documentation of CAS within the GeCAS registry, the nationwide and obligatory documentation is strictly focused on the main issues, such as indications and between hospital comparisons of outcome of patients. In the GeCAS registry data collection is generally more extensive and also includes a 30-day and 10-year follow-up. Compared to the BQS institute, benchmarking reports of GeCAS are more detailed and are made available to every participating hospital on a biannual basis. This generates an image of the current reality of CAS in Germany in addition to the nationwide obligatory documentation. Furthermore, data of the GeCAS registry is the basis for research work (e.g. publications and presentations), for generating new hypotheses and for technical development in CAS in Germany. Consequently, the existence of a multicenter and multidisciplinary CAS registry, such as the GeCAS registry, is considered necessary and medically useful.

Hintergrund Die aktuellen Leitlinien der Europaischen Gesellschaft fur Kardiologie (ESC) empfehlen die Bildung von regionalen Netzwerken zur optimierten Versorgung von Patienten mit akutem ST-Streckenhebungsmyokardinfarkt (STEMI).

Approximately 50 % of hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and up to 80 % of patients with infarction-related cardiogenic shock have multivessel coronary artery disease. The optimal revascularization strategy in these patients has still not been defined. Following successful percutaneous coronary intervention (PCI) of the culprit lesion, immediate PCI of all additional lesions or staged PCI, after invasive or non-invasive proof of ischemia or conservative therapy can be considered. Randomized studies have demonstrated a clinical benefit of immediate or staged multivessel PCI compared to a conservative approach. So far there are no randomized studies available comparing immediate versus staged PCI. The data regarding the optimal strategy in patients with cardiogenic shock show low concordance. The currently running CULPRIT shock study will help to define the optimal strategy in shock patients. This manuscript summarizes the current knowledge and data and provides recommendations for the clinical practice.