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Patients with COPD often have reduced physical activity, which can impair health status. Real-world data can provide valuable information on the health and functional status of patients with COPD treated with tiotropium/olodaterol. AERIAL® (ClinicalTrials.gov NCT03165045) was a German, non-interventional study of patients with COPD receiving treatment with tiotropium/olodaterol under real-world conditions for ∼6 weeks. The primary end-point was the proportion of patients achieving a decrease of ≥0.4 points in Clinical COPD Questionnaire (CCQ) score. The CCQ-4 subdomain was used to assess functional status, and the Physician's Global Evaluation (PGE) scale was used to assess the patients’ general condition. Safety was assessed, as well as patient satisfaction and willingness to continue treatment. Out of 1351 screened patients, 1322 were treated and 1140 comprised the full analysis set. The primary end-point was met: 66.3% of patients achieved a ≥0.4-point decrease in overall CCQ score (mean±sd decrease 0.78±0.95). Mean±sd decreases in CCQ symptoms and functional state subdomains were 0.84±1.06 and 0.75±1.05 points, respectively. PGE scores improved. One fatality (not treatment-related) and 23 drug-related adverse events were recorded, most commonly nausea and vertigo. >85% of patients were satisfied/very satisfied with tiotropium/olodaterol overall and with the Respimat® device, both in terms of inhalation and handling. Most patients (95.2%) expressed willingness to continue treatment. Patients with COPD treated with tiotropium/olodaterol via Respimat® in routine clinical practice had clinically relevant improvements in health and functional status compared with baseline., The AERIAL non-interventional study demonstrated that patients with COPD treated with tiotropium/olodaterol via Respimat in routine clinical practice had high product satisfaction and clinically relevant improvements in health and functional status https://bit.ly/3jf6hIf

Background Patients with chronic obstructive pulmonary disease (COPD) show signs of reduced physical activity from the early stages of the disease, impacting morbidity and mortality. Data suggest treatment with tiotropium, a long-acting muscarinic antagonist, and olodaterol, a long-acting s2-agonist (LABA), as monotherapies and in combination, increases exercise capacity. This study assessed the effects of fixed-dose tiotropium/olodaterol (delivered via Respimat®) on physical function in Global Initiative for Chronic Obstructive Lung Disease A-D patients requiring long-acting dual bronchodilation treatment in a real-world setting. Methods This open-label, single arm, noninterventional study measured changes in physical function in COPD patients treated with tiotropium/olodaterol 5/5 μg for approximately 6 weeks (between Visit 1 [baseline] and Visit 2). Primary end point was therapeutic success, defined as a minimum 10-point increase in Physical Functioning Questionnaire (PF-10) score. Secondary end points included change in PF-10 from Visit 1 to Visit 2, the patient's general condition (measured by Physician's Global Evaluation score) at Visit 1 and Visit 2, and patient satisfaction with treatment delivered via the Respimat® device (assessed by Patient Satisfaction Questionnaire) at study end. Results Therapeutic success was observed in 51.5% of 1578 patients (95% confidence interval [CI] 49.0, 54.0) after approximately 6 weeks of treatment with tiotropium/olodaterol. Mean change in PF-10 score between Visit 1 and Visit 2 was 11.6 points (95% CI 10.7, 12.6). Patient general condition improved as indicated by a general improvement in scores between visits. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment (82.5%), inhalation (87.5%), and handling of Respimat® (85.2%). One percent of patients reported an investigator-defined drug-related adverse events (AE). Conclusion Tiotropium/olodaterol treatment improved physical functioning in COPD patients. An associated increase in patient general condition was observed. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment, inhaling, and handling of the Respimat® device. No unexpected drug-related AE occurred.

In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to the definition, clinical classification and initial diagnosis of PH. While the European guidelines provide a detailed clinical classification and a structured approach for diagnostic testing, their application in routine care may be challenging, particularly given the changing phenotype of PH patients who are nowadays often elderly and may present with multiple potential causes of PH, as well as comorbid conditions. Specifically, the working group addresses the thoroughness of diagnostic testing, and the roles of echocardiography, exercise testing, and genetic testing in diagnosing PH. Furthermore, challenges in the diagnostic work-up of patients with various causes of PH including “PAH with comorbidities”, CTEPH and coexisting conditions are highlighted, and a modified diagnostic algorithm is provided. The detailed results and recommendations of the working group on definition, clinical classification and initial diagnosis of PH, which were last updated in the spring of 2018, are summarized in this article.

Crowdfunding has become a serious opportunity for financing sustainable entrepreneurship. However, funders oftentimes compete with several similar projects for funding. In crowdfunding, projects are only realized if they reach a minimum funding threshold, and this means that funders need to coordinate to reach such a threshold. In this study, we examine how different types of sustainability seals help solve this coordination problem. We simulate a crowdfunding situation using a threshold public goods laboratory experiment. Our results show that the choice of a signal is sensitive to the type of crowdfunding project. For a sustainability project, a non-governmental seal is a better match. Our findings offer new insights for innovators, entrepreneurs, and institutions on how to obtain contributions for sustainability projects and ultimately bring more of this type of project to life.

Covalent modification of proteins with the small ubiquitin-related modifier (SUMO) is found in all eukaryotes and is involved in many important processes. SUMO attachment may change interaction properties, subcellular localization, or stability of a modified protein. Usually, only a small fraction of a protein is modified at a given time because sumoylation is a highly dynamic process. The sumoylated state of a protein is controlled by the activity of the sumoylation enzymes that promote either their mono- or poly-sumoylation (SUMO chain formation), by SUMO proteases that reverse these modifications, and by SUMO-targeted ubiquitin ligases (STUbL, ULS) that mediate their degradation by the proteasome. While some organisms, such as humans, express multiple isoforms, budding yeast SUMO is encoded by a single and essential gene termed SMT3. The analysis of the simpler SUMO system in budding yeast has been instrumental in the identification of enzymes acting on this modification and controlling its dynamics. Sumoylation of proteins changes dramatically during the cell division cycle and under various stress conditions. Here we summarize various approaches that employ Saccharomyces cerevisiae as a model system to study the dynamics of sumoylation and how it is controlled.

Covalent modification of proteins with the small ubiquitin-related modifier (SUMO) is found in all eukaryotes and is involved in many important processes. SUMO attachment may change interaction properties, subcellular localization, or stability of a modified protein. Usually, only a small fraction of a protein is modified at a given time because sumoylation is a highly dynamic process. The sumoylated state of a protein is controlled by the activity of the sumoylation enzymes that promote either their mono- or poly-sumoylation (SUMO chain formation), by SUMO proteases that reverse these modifications, and by SUMO-targeted ubiquitin ligases (STUbL, ULS) that mediate their degradation by the proteasome. While some organisms, such as humans, express multiple isoforms, budding yeast SUMO is encoded by a single and essential gene termed SMT3. The analysis of the simpler SUMO system in budding yeast has been instrumental in the identification of enzymes acting on this modification and controlling its dynamics. Sumoylation of proteins changes dramatically during the cell division cycle and under various stress conditions. Here we summarize various approaches that employ Saccharomyces cerevisiae as a model system to study the dynamics of sumoylation and how it is controlled.

We exploit high-order harmonic generation spectroscopy at the caustics of the recombining electron wave-packet as a method for directly comparing experimental spectra with ab-initio theories. Experimental results in xenon and comparison with ab-initio time-dependent configuration-interaction singles calculations allowed to assess the role of the wave-packet enhancement during the giant resonance. Results in argon show that this technique can also be applied to other targets.

Die 2015 veroffentlichten Europaischen Leitlinien zur Diagnostik und Therapie der pulmonalen Hypertonie (PH) sind nunmehr auch in Deutschland gultig. Die Leitlinien befassen sich eingehend mit der Klassifikation und Diagnostik der PH, und bieten daruber hinaus neue Empfehlungen zur Risikostratifizierung und Verlaufskontrollen bei Patienten mit diagnostizierter PAH. Fur die praktische Umsetzung der Europaischen Leitlinien in Deutschland sind jedoch zahlreiche fur Deutschland spezifische Gesichtspunkte und bereits wieder neue Daten bedeutsam, die eine ausfuhrliche Kommentierung der Leitlinien und in einigen Punkten eine Aktualisierung notwendig machen. Im Juni 2016 fand in Koln eine Konsensus-Konferenz statt, die von den Arbeitsgruppen PH der Deutschen Gesellschaften fur Kardiologie (DGK), Pneumologie (DGP) und Padiatrische Kardiologie (DGPK) organisiert wurde. Die Konferenz befasste sich mit der Umsetzung der Europaischen Leitlinien im deutschsprachigen Raum. Dazu wurden verschiedene Arbeitsgruppen eingesetzt, von denen sich eine gezielt der Klassifikation und initialen Diagnostik der PH widmete. Die Ergebnisse und Beschlusse dieser Arbeitsgruppe werden in dem vorliegenden Manuskript detailliert beschrieben.

A cumulative analysis of both PULSAR trials would demonstrate sarcoidosis-associated pulmonary hypertension proven by right heart catheter in 15/510 patients and precapillary PH in 13/510 patientshttp://bit.ly/34VGWbv

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype–Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular–cardiac–cutaneous–central nervous system disease involvement, 3) musculoskeletal–cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.

Spectral focusing of the recolliding electron in high-order harmonic generation driven by two-color fields is shown to be a powerful tool for isolating and enhancing hidden spectral features of the target under study. In previous works we used this technique for probing multi-electron effects in xenon and we compared our experimental results with time-dependent configuration-interaction singles calculations. We demonstrate here that this technique can be exploited for reconstructing the enhancement factor of the xenon giant dipole resonance and we discuss the sensitivity of this method to macroscopic effects. We then extend the technique to argon in order to test the applicability of this procedure to other targets.

The generation of therapeutic antibodies with extremely high affinities down to the low picomolar range is today feasible with state-of-the art recombinant technologies. However, reliable and efficient identification of lead candidates with the desired affinity from a pool of thousands of antibody clones remains a challenge. Here, we describe a high-throughput procedure that allows reliable affinity screening of unpurified immunoglobulin G or antibody fragments. The method is based on the principle of solution equilibrium titration (SET) using highly sensitive electrochemiluminescence as a readout system. Because the binding partners are not labeled, the resulting KD represents a sound approximation of the real affinity. For screening, diluted bacterial lysates or cell culture supernatants are equilibrated with four different concentrations of a soluble target molecule, and unbound antibodies are subsequently quantified on 384-well Meso Scale Discovery (MSD) plates coated with the respective antigen. For determination of KD values from the resulting titration curves, fit models deduced from the law of mass action for 1:1 and 2:1 binding modes are applied to assess hundreds of interactions simultaneously. The accuracy of the method is demonstrated by comparing results from different screening campaigns from affinity optimization projects with results from detailed affinity characterization.

Objectives While idiopathic pulmonary arterial hypertension (PAH) is a rare disease, it is seen more frequently in patients with HIV infection. The aim of this study was to evaluate the prevalence of pulmonary hypertension (PH) in patients with HIV infection by echocardiographic screening. Methods Echocardiography and N-terminal of the prohormone brain natriuretic peptide measurement were used to examine the prevalence of PH prospectively in HIV-positive patients (n = 374) during routine follow-up visits for HIV disease. Results In echocardiographic screening, PH was detected in a total of 23 of 374 HIV-infected patients (6.1%). Of these, three patients (13%) presented with symptoms of dyspnoea and fatigue, and diagnosis of PAH was confirmed by right heart catheterization. Patients with systolic pulmonary artery pressure (sPAP) > 30 mmHg were more likely to be female, to have a history of injecting drug use and to originate from high-prevalence countries (HPCs). Conclusions Echocardiographic screening detected PH in a substantial proportion of HIV-positive patients. Female gender, a history of injecting drug use and HPC origin were associated with a higher prevalence of HIV-associated PH. The relevance and long-term outcome of these findings need to be validated in follow-up studies, which are ongoing.

We investigate the sub-femtosecond dynamics of a highly excited xenon atom coherently driven by a strong control field at which the Rabi frequency of the system is comparable to the frequency of a driving laser. The widely used rotating wave approximation (RWA) breaks down at such fields, resulting in new features such as counter rotating wave (CRW) effect. We present the first time-resolved observation of the CRW effect motion in the highly excited 4d−1np xenon using using attosecond transient absorption spectroscopy (ATAS). Time-dependent many-body theory confirms the observation and explains the various features of the absorption spectrum seen in experiment.

Nature Communications 8(1), 453(2017). doi:10.1038/s41467-017-00426-6, Ultrafast proton migration and isomerization are key processes for acetylene and its ions. However, the mechanism for ultrafast isomerization of acetylene [HCCH]$^{2+}$to vinylidene [H$_2$CC]$^{2+}$ dication remains nebulous. Theoretical studies show a large potential barrier (> 2 eV) for isomerization on low-lying dicationic states, implying picosecond or longer isomerization timescales. However, a recent experiment at a femtosecond X-ray free-electron laser suggests sub-100 fs isomerization. Here we address this contradiction with a complete theoretical study of the dynamics of acetylene dication produced by Auger decay after X-ray photoionization of the carbon atom K shell. We find no sub-100 fs isomerization, whilereproducing the salient features of the time-resolved Coulomb imaging experiment. This work resolves the seeming contradiction between experiment and theory and also calls forcareful interpretation of structural information from the widely applied Coulomb momentum imaging method., Published by Nature Publishing Group, London

We investigate the subfemtosecond dynamics of a highly excited xenon atom coherently driven by a strong control field at which the Rabi frequency of the system is comparable to the frequency of a driving laser. The widely used rotating-wave approximation breaks down at such fields, resulting in features such as the counter-rotating-wave (CRW) effect. We present a time-resolved observation of the CRW effect in the highly excited $4{d}^{\ensuremath{-}1}np$ xenon using attosecond transient absorption spectroscopy. Time-dependent many-body theory confirms the observation and explains the various features of the absorption spectrum seen in experiment.

Attosecond x-ray pulses offer unprecedented opportunities for probing and triggering new types of ultrafast motion. At the same time, pulse characterization of x-rays presents new challenges that do not exist in the UV regime. Inner-shell ionization is the dominant ionization mechanism for x-rays and it is followed by secondary processes like fluorescence, Auger decay, and shake-up.In general, we find that inner-shell ionization and secondary processes can create additional delay-dependent modulations that will affect pulse reconstruction schemes. Our recently proposed pulse characterization method [Pabst and Dahlstr\"om, PRA 94, 013411 (2016)], where a bound electron wavepacket is sequentially photoionized by the attosecond pulse, can be adapted to mitigate the impact of these effects, thus opening up an avenue for reliable pulse reconstruction in the x-ray regime., Comment: 8 figures

Physical Review A, 95 (1), ISSN:1094-1622, ISSN:0556-2791, ISSN:1050-2947

Atoms constitute relatively simple many-body systems, making them suitable objects for developing an understanding of basic aspects of many-body physics. Photoabsorption spectroscopy is a prominent method to study the electronic structure of atoms and the inherent many-body interactions. In this article the impact of many-body effects on well-known spectroscopic features such as Rydberg series, Fano resonances, Cooper minima, and giant resonances is studied, and related many-body phenomena in other fields are outlined. To calculate photoabsorption cross sections the time-dependent configuration interaction singles (TDCIS) model is employed. The conceptual clearness of TDCIS in combination with the compactness of atomic systems allows for a pedagogical introduction to many-body phenomena., 15 pages, 6 figures, 1 table. The following article has been accepted by American Journal of Physics

Anamnese und klinischer Befund: Ein 49-jahriger Patient wurde aufgrund akuter typischer Angina pectoris bei Nicht-ST-Hebungsinfarkt aus der HNO-Klink eines auswartigen Krankenhauses aufgenommen. Dort war aufgrund einer chronischen Rhinitis und Epistaxis rhinoskopisch eine Biopsie entnommen worden. Diese hatte das histologische Bild einer Granulomatose mit Polyangiitis (fruher: Morbus Wegener) gezeigt. Untersuchungen: Die Koronarangiographie ergab eine koronare Eingefaserkrankung ohne hohergradige interventionspflichtige Stenosen. In der transthorakalen Echokardiographie zeigte sich eine diastolische Dysfunktion sowie ein hamodynamisch nicht relevanter Perikarderguss. In der Kernspintomographie des Herzens fanden sich multiple Myokardnekrosen gekennzeichnet durch umschriebene, fleckformige Kontrastmittelanreicherungen mittventrikular septal und apikal. Bei beidseitigen disseminierten nodularen Verdichtungen mit teils zentraler Einschmelzung in der thorakalen Computertomographie sowie Mikrohamaturie, Leukozyturie und Proteinurie musste von einer Multiorganbeteiligung bei einer Granulomatose mit Polyangiitis ausgegangen werden. Therapie und Verlauf: Unter einer oralen Kortisontherapie sowie Gabe von Cyclophosphamid kam es zu einer raschen Besserung der klinischen Symptomatik sowie der Laborparameter. Folgerungen: Die Prognose der Granulomatose mit Polyangiitis ist hauptsachlich durch die pulmonale und renale Beteiligung determiniert. Eine kardiale Beteiligung ist selten und sollte vor allem bei chronischen therapierefraktaren Verlaufen in Betracht gezogen werden. Da nahezu alle kardialen Strukturen betroffen sein konnen, drohen vielgestaltige, teils ernste Komplikationen. In der Regel spricht die Granulomatose mit Polyangiits gut auf eine immunsuppressive Therapie an.

We propose a technique to fully characterize the temporal structure of extreme ultraviolet pulses by ionizing a bound coherent electronic wave packet. The influence of the dipole phase, which is the main obstacle for state-of-the-art pulse characterization schemes, can be eliminated by angle integration of the photoelectron spectrum. We show that in particular, atomic Rydberg wave packets are ideal and that wave packets involving multiple electronic states provide redundant information that can be used to cross-check the consistency of the phase reconstruction.

We investigated the giant resonance in Xenon by high-order harmonic generation spectroscopy driven by a two-color field. The addition of a non-perturbative second harmonic component parallel to the driving field breaks the symmetry between neighboring sub-cycles resulting in the appearance of spectral caustics at two distinct cut-off energies. By controlling the phase delay between the two color components it is possible to tailor the harmonic emission in order to amplify and isolate the spectral feature of interest. In this paper we demonstrate how this control scheme can be used to investigate the role of electron correlations that give birth to the giant resonance in Xenon. The collective excitations of the giant dipole resonance in Xenon combined with the spectral manipulation associated with the two color driving field allow to see features that are normally not accessible and to obtain a quantitative good agreement between the experimental results and the theoretical predictions.

XUV nonlinear spectroscopy has recently discovered that there is more than one collective dipole resonance state in the energy range of the giant dipole resonance (GDR) of atomic Xe. This resonance-state substructure, hidden in the linear regime, raises imminent questions regarding our understanding of the collective electronic behavior of Xe, which has been largely founded on linear spectroscopic studies. Here, we approach the collective response of Xe from a new perspective: we study directly the resonance eigenstates, and then analyze their spectroscopic manifestations. We find that linear spectroscopy captures only partial information on the resonance substructure as a result of quantum interferences. Moreover, we show that the resonance state dominating the GDR in linear spectroscopy has no adiabatic connection to the resonance state governing the corresponding cross section when multielectron interactions are neglected. Going beyond the dipole-allowed correlated electronic structure, we predict the existence of collective multipole resonances of Xe. Unlike any known collective feature in atoms, these resonances live exceptionally long (more than 100 attoseconds), thus providing a new playground for studying the collective nonlinear response of Xe using advanced light sources.

We investigate the behavior of several spatial grid methods and complex absorbers for strong-field and attosecond scenarios when using the time-dependent configuration-interaction singles method to solve the multi-electron time-dependent Schr\"odinger equation for atoms. We compare the pseudospectral grid, finite-element, and finite-element-discrete-variable-representation (DVR) methods with each other and discuss their advantages and disadvantages. Additionally, we study the performances of complex absorbing potential (CAP) and smooth exterior complex scaling (SES) to absorb the outgoing electron. We find that SES performs generally better than CAP for calculating high-harmonic generation spectra and XUV photoelectron spectra. In both of these cases, the DVR and even more the FEM grid representations show more reliable results\char22{}especially when using SES. Both absorbers show drawbacks when calculating photoelectron spectra in the strong-field regime.

Physical Review A, 93 (2), ISSN:1094-1622, ISSN:0556-2791, ISSN:1050-2947

We probed the electronic structure of xenon by two-color high-order harmonic spectroscopy. We were able to identify the contribution of electron correlations in the spectral region corresponding to the giant resonance.

Rationale: Sarcoidosis is a complex inflammatory disease with a heterogeneous clinical picture. Among others, an acute and chronic clinical course can be distinguished, for which specific genetic risk factors are known. Objectives: To identify additional risk loci for sarcoidosis and its acute and chronic subforms, we analyzed imputed data from a genomewide association scan for these phenotypes. Methods: After quality control, the genome-wide association scan comprised nearly 1.3 million imputed single-nucleotide polymorphisms based on an Affymetrix 6.0 Gene Chip dataset of 564 German sarcoidosis cases, including 176 acute and 354 chronic cases and 1,575 control subjects. Measurements and Main Results: We identified chromosome 11q13.1 (rs479777) as a novel locus influencing susceptibility to sarcoidosis with genome-wide significance. The marker was significantly associated in three distinct German case-control populations and in an additional German family sample with odds ratios ranging from 0.67 to 0.77. This finding was further replicated in two independent European case-control populations from the Czech Republic (odds ratio, 0.75) and from Sweden (odds ratio, 0.79). In a meta-analysis of the included European case-control samples the marker yielded a P value of 2.68 x 10(-18). The locus was previously reported to be associated with Crohn disease, psoriasis, alopecia areata, and leprosy. For sarcoidosis, fine-mapping and expression analysis suggest KCNK4, PRDX5, PCLB3, and most promising CCDC88B as candidates for the underlying risk gene in the associated region. Conclusions: This study provides striking evidence for association of chromosome 11q13.1 with sarcoidosis in Europeans, and thus identified a further genetic risk locus shared by sarcoidosis, Crohn disease and psoriasis.

Anamnese und klinischer Befund: Eine 53-jahrige Patientin wurde aufgrund eines akuten Koronarsyndroms (NSTEMI) in unserer Chest-Pain-Unit aufgenommen. Anamnestisch waren chronische Sinusitiden und ein allergisches Asthma bekannt, zudem bestand eine B-Symptomatik in den vergangenen 6 Monaten. Untersuchungen: Koronarangiographisch wurde eine koronare Makroangiopathie ausgeschlossen. Die transthorakale Echokardiographie zeigte einen hamodynamisch nicht relevanten Perikarderguss sowie eine septal-apikale Kinetikstorung, woraufhin eine Kernspintomographie des Herzens durchgefuhrt wurde. Diese ergab eine mit einer Vaskulitis vereinbare subendokardiale Myokardnarbe. Die Computertomographie zeigten zusatzlich pulmonale Infiltrate, in der Labordiagnostik fiel eine Eosinophilie auf, weshalb die klinische Diagnose einer Churg-Strauss-Vaskulitis (CSV) mit entzundlicher kardialer Beteiligung gestellt wurde. Therapie und Verlauf: Unter einer oralen Steroidtherapie kam es zu einer raschen Besserung der klinischen Symptomatik sowie der Laborparameter. Folgerungen: Vor allem bei jungeren Patienten mit Asthma und Eosinophilie ohne klassisches kardiales Risikoprofil sollte eine Vaskulitis neben einer Myokarditis als wichtige Differenzialdiagnose einer Troponinerhohung bei unauffalligem Koronarbefund in Betracht gezogen werden. In der Regel spricht eine Churg-Strauss-Vaskulitis gut auf eine immunsuppressive Therapie an.

longed hyperglycemia over the subsequent hospital stay is further supporting the above speculation [4,5]. In our own opinion patients admitted with hyperglycemia warrant close assessment. Such assessment includes close surveillance of their in hospital blood sugar, check their glycated hemoglobin, rule out hidden diabetes and even screen target organ involvement. Regarding the role of tight glycemic control in patients with diabetes it seems each patient should receive a well-defined plan and risk stratification based on the severity of his target organ involvement, duration of diabetes and the integrity of his cardiovascular compartment. The literature suggests that those with early-diagnosed diabetes, i.e. those with the shortest duration should have their sugar strictly controlled. The long-term outcome of such patients seems to be extremely favorable in terms of macro and microvascular complication. Another group of patients whom tight glycemic control strategy is potential the so called the escapers. The escapers referred to patients with long duration of diabetes who escaped the major diabetic morbidities. The exciting data that define their characteristics are still awaited [6]. The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology (Shewan and Coats 2010; 144: 1–2).

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the non-invasive diagnosis of pulmonary hypertension. This manuscript describes in detail the results and recommendations of the working group which were last updated in October 2011.

Sarcoidosis can evolve into a chronic disease with persistent granulomas accompanied by progressive fibrosis. While an unlimited inflammatory response suggests an impaired immune control in sarcoid lesions, it stands in contrast to the massive infiltration with CD4(+)CD25(high)FoxP3(+) regulatory T cells. We here revealed that those Treg cells in affected lung lesions were mainly derived from activated natural Treg cells with GARP (LRRC32)-positive phenotype but exhibited reduced repressor capacities despite high IL-10 and TGF-beta 1 levels. The repressive capacity of blood Treg cells, in contrast, was not impaired compared to age-matched healthy donors. Treg derived cells in granuloma lesions have undergone extensive rounds of amplifications indicated by shortened telomeres compared to blood Treg cells of the same patient. Lesional Treg derived cells moreover secreted pro-inflammatory cytokines including IL-4 which sustains granuloma formation through fibroblast amplification and the activation of mast cells, the latter indicated by the expression of membrane-bound oncostatin M.

History Within three months, three patients with end-stage renal disease presented for evaluation of pulmonary hypertension (PH): a 72-year-old woman (case 1), a 67-year-old patient (case 2) and a 75-year-old patient (case 3), each with increasing dyspnea (WHO functional class III). Investigations In all three cases, there was echocardiographic evidence of right heart failure; right heart catheterization was completed before and after dialysis. In case 1, we found a postcapillary PH (PH group 2 - PH with left heart diseases/diastolic dysfunction). Case 2 also showed a postcapillary PH and a high cardiac output of 9.7 l/min. In case 3, unmasked after dialysis, a precapillary, pulmonary arterial hypertension (PAH - group 1) was detected. Treatment and course In patient 1, no relevant improvement of symptoms was observed, despite optimized cardiac therapy. There was a significant clinical improvement in patient 2 after surgical reduction of the arteriovenous shunt. In patient 3, relevant clinical and hemodynamic improvement was seen under treatment with bosentan. Conclusion These cases confirm the role of right heart catheterization in the differential diagnosis of unclear PH in patients with end-stage renal failure. Moreover, the three cases point to three different causes. Specific therapies can result in significant symptomatic improvement.