@article{FreyGassenmaierHofmannetal.2020, author = {Frey, Anna and Gassenmaier, Tobias and Hofmann, Ulrich and Schmitt, Dominik and Fette, Georg and Marx, Almuth and Heterich, Sabine and Boivin-Jahns, Val{\´e}rie and Ertl, Georg and Bley, Thorsten and Frantz, Stefan and Jahns, Roland and St{\"o}rk, Stefan}, title = {Coagulation factor XIII activity predicts left ventricular remodelling after acute myocardial infarction}, series = {ESC Heart Failure}, volume = {7}, journal = {ESC Heart Failure}, number = {5}, doi = {10.1002/ehf2.12774}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236013}, pages = {2354-2364}, year = {2020}, abstract = {Aims Acute myocardial infarction (MI) is the major cause of chronic heart failure. The activity of blood coagulation factor XIII (FXIIIa) plays an important role in rodents as a healing factor after MI, whereas its role in healing and remodelling processes in humans remains unclear. We prospectively evaluated the relevance of FXIIIa after acute MI as a potential early prognostic marker for adequate healing. Methods and results This monocentric prospective cohort study investigated cardiac remodelling in patients with ST-elevation MI and followed them up for 1 year. Serum FXIIIa was serially assessed during the first 9 days after MI and after 2, 6, and 12 months. Cardiac magnetic resonance imaging was performed within 4 days after MI (Scan 1), after 7 to 9 days (Scan 2), and after 12 months (Scan 3). The FXIII valine-to-leucine (V34L) single-nucleotide polymorphism rs5985 was genotyped. One hundred forty-six patients were investigated (mean age 58 ± 11 years, 13\% women). Median FXIIIa was 118 \% (quartiles, 102-132\%) and dropped to a trough on the second day after MI: 109\%(98-109\%; P < 0.001). FXIIIa recovered slowly over time, reaching the baseline level after 2 to 6 months and surpassed baseline levels only after 12 months: 124 \% (110-142\%). The development of FXIIIa after MI was independent of the genotype. FXIIIa on Day 2 was strongly and inversely associated with the relative size of MI in Scan 1 (Spearman's ρ = -0.31; P = 0.01) and Scan 3 (ρ = -0.39; P < 0.01) and positively associated with left ventricular ejection fraction: ρ = 0.32 (P < 0.01) and ρ = 0.24 (P = 0.04), respectively. Conclusions FXIII activity after MI is highly dynamic, exhibiting a significant decline in the early healing period, with reconstitution 6 months later. Depressed FXIIIa early after MI predicted a greater size of MI and lower left ventricular ejection fraction after 1 year. The clinical relevance of these findings awaits to be tested in a randomized trial.}, language = {en} } @article{GabrielJirůHillmannKraftetal.2020, author = {Gabriel, Katharina M. A. and J{\´i}rů-Hillmann, Steffi and Kraft, Peter and Selig, Udo and R{\"u}cker, Victoria and M{\"u}hler, Johannes and D{\"o}tter, Klaus and Keidel, Matthias and Soda, Hassan and Rascher, Alexandra and Schneider, Rolf and Pfau, Mathias and Hoffmann, Roy and Stenzel, Joachim and Benghebrid, Mohamed and Goebel, Tobias and Doerck, Sebastian and Kramer, Daniela and Haeusler, Karl Georg and Volkmann, Jens and Heuschmann, Peter U. and Fluri, Felix}, title = {Two years' experience of implementing a comprehensive telemedical stroke network comprising in mainly rural region: the Transregional Network for Stroke Intervention with Telemedicine (TRANSIT-Stroke)}, series = {BMC Neurology}, volume = {20}, journal = {BMC Neurology}, doi = {10.1186/s12883-020-01676-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229214}, year = {2020}, abstract = {Background Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive telemedical stroke network comprising all levels of stroke care in a defined region. Methods The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals. Results Overall, 7881 patients were included (mean age 74.6 years +/- 12.8; 48.4\% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31\%), mainly in secondary stroke prevention; b) improvement over time (44\%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25\%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period. Conclusion The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals.}, language = {en} } @article{ElabyadTerekhovLohretal.2020, author = {Elabyad, Ibrahim A. and Terekhov, Maxim and Lohr, David and Stefanescu, Maria R. and Baltes, Steffen and Schreiber, Laura M.}, title = {A Novel Mono-surface Antisymmetric 8Tx/16Rx Coil Array for Parallel Transmit Cardiac MRI in Pigs at 7T}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-020-59949-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229436}, year = {2020}, abstract = {A novel mono-surface antisymmetric 16-element transmit/receive (Tx/Rx) coil array was designed, simulated, constructed, and tested for cardiac magnetic resonance imaging (cMRI) in pigs at 7T. The cardiac array comprised of a mono-surface 16-loops with two central elements arranged antisymmetrically and flanked by seven elements on either side. The array was configured for parallel transmit (pTx) mode to have an eight channel transmit and 16-channel receive (8Tx/16Rx) coil array. Electromagnetic (EM) simulations, bench-top measurements, phantom, and MRI experiments with two pig cadavers (68 and 46 kg) were performed. Finally, the coil was used in pilot in-vivo measurements with a 60 kg pig. Flip angle (FA), geometry factor (g-factor), signal-to-noise ratio (SNR) maps, and high-resolution cardiac images were acquired with an in-plane resolution of 0.6 mm x 0.6 mm (in-vivo) and 0.3 mm x 0.3 mm (ex-vivo). The mean g-factor over the heart was 1.26 (R = 6). Static phase B-1(+) shimming in a pig body phantom with the optimal phase vectors makes possible to improve the B-1(+) homogeneity by factor > 2 and transmit efficiency by factor > 3 compared to zero phases (before RF shimming). Parallel imaging performed in the in-vivo measurements demonstrated well preserved diagnostic quality of the resulting images at acceleration factors up to R = 6. The described hardware design can be adapted for arrays optimized for animals and humans with a larger number of elements (32-64) while maintaining good decoupling for various MRI applications at UHF (e.g., cardiac, head, and spine).}, language = {en} } @article{KolokotronisPlutaKlopockietal.2020, author = {Kolokotronis, Konstantinos and Pluta, Natalie and Klopocki, Eva and Kunstmann, Erdmute and Messroghli, Daniel and Maack, Christoph and Tejman-Yarden, Shai and Arad, Michael and Rost, Simone and Gerull, Brenda}, title = {New Insights on Genetic Diagnostics in Cardiomyopathy and Arrhythmia Patients Gained by Stepwise Exome Data Analysis}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {7}, doi = {10.3390/jcm9072168}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236094}, year = {2020}, abstract = {Inherited cardiomyopathies are characterized by clinical and genetic heterogeneity that challenge genetic diagnostics. In this study, we examined the diagnostic benefit of exome data compared to targeted gene panel analyses, and we propose new candidate genes. We performed exome sequencing in a cohort of 61 consecutive patients with a diagnosis of cardiomyopathy or primary arrhythmia, and we analyzed the data following a stepwise approach. Overall, in 64\% of patients, a variant of interest (VOI) was detected. The detection rate in the main sub-cohort consisting of patients with dilated cardiomyopathy (DCM) was much higher than previously reported (25/36; 69\%). The majority of VOIs were found in disease-specific panels, while a further analysis of an extended panel and exome data led to an additional diagnostic yield of 13\% and 5\%, respectively. Exome data analysis also detected variants in candidate genes whose functional profile suggested a probable pathogenetic role, the strongest candidate being a truncating variant in STK38. In conclusion, although the diagnostic yield of gene panels is acceptable for routine diagnostics, the genetic heterogeneity of cardiomyopathies and the presence of still-unknown causes favor exome sequencing, which enables the detection of interesting phenotype-genotype correlations, as well as the identification of novel candidate genes.}, language = {en} } @article{HoffmannJanssenKannoetal.2020, author = {Hoffmann, Jan V. and Janssen, Jan P. and Kanno, Takayuki and Shibutani, Takayuki and Onoguchi, Masahisa and Lapa, Constantin and Grunz, Jan-Peter and Buck, Andreas K. and Higuchi, Takahiro}, title = {Performance evaluation of fifth-generation ultra-high-resolution SPECT system with two stationary detectors and multi-pinhole imaging}, series = {EJNMMI Physics}, volume = {7}, journal = {EJNMMI Physics}, doi = {10.1186/s40658-020-00335-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230361}, year = {2020}, abstract = {Background Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT\(^+\)). Methods The new U-SPECT5-E with two stationary detectors was used for acquiring data with \(^{99m}\)Tc-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT\(^+\) for comparison. Results Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT\(^+\). In the visually analysed sections of the reconstructed mini Derenzo phantoms, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7\% (XUHR-M), 29.1\% (GP-M, U-SPECT5-E), 16.3\% (GP-M, U-SPECT\(^+\)) and 23.0\% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60 to 1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR. Conclusions While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup.}, language = {en} } @article{GrebeMalzahnDonhauseretal.2020, author = {Grebe, S{\"o}ren Jendrik and Malzahn, Uwe and Donhauser, Julian and Liu, Dan and Wanner, Christoph and Krane, Vera and Hammer, Fabian}, title = {Quantification of left ventricular mass by echocardiography compared to cardiac magnet resonance imaging in hemodialysis patients}, series = {Cardiovascular Ultrasound}, volume = {18}, journal = {Cardiovascular Ultrasound}, doi = {10.1186/s12947-020-00217-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229282}, year = {2020}, abstract = {Background: Left ventricular hypertrophy (LVH), defined by the left ventricular mass index (LVMI), is highly prevalent in hemodialysis patients and a strong independent predictor of cardiovascular events. Compared to cardiac magnetic resonance imaging (CMR), echocardiography tends to overestimate the LVMI. Here, we evaluate the diagnostic performance of transthoracic echocardiography (TTE) compared to CMR regarding the assessment of LVMI in hemodialysis patients. Methods: TTR and CMR data for 95 hemodialysis patients who participated in the MiREnDa trial were analyzed. The LVMI was calculated by two-dimensional (2D) TTE-guided M-mode measurements employing the American Society of Echocardiography (ASE) and Teichholz (Th) formulas, which were compared to the reference method, CMR. Results: LVH was present in 44\% of patients based on LVMI measured by CMR. LVMI measured by echocardiography correlated moderately with CMR, ASE: r = 0.44 (0.34-0.62); Th: r = 0.44 (0.32-0.62). Compared to CMR, both echocardiographic formulas overestimated LVMI (mean increment LVMI (ASE-CMR): 19.5 +/- 19.48 g/m(2),p < 0.001; mean increment LVMI (Th-CMR): 15.9 +/- 15.89 g/m(2),p < 0.001). We found greater LVMI overestimation in patients with LVH using the ASE formula compared to the Th formula. Stratification of patients into CMR LVMI quartiles showed a continuous decrease in increment LVMI with increasing CMR LVMI quartiles for the Th formula (p < 0.001) but not for the ASE formula (p = 0.772). Bland-Altman analysis showed that the Th formula had a constant bias independent of LVMI. Both methods had good discrimination ability for the detection of LVH (ROC-AUC: 0.819 (0.737-0.901) and 0.808 (0.723-0.892) for Th and ASE, respectively). Conclusions: The ASE and Th formulas overestimate LVMI in hemodialysis patients. However, the overestimation is less with the Th formula, particularly with increasing LVMI. The results suggest that the Th formula should be preferred for measurement of LVMI in chronic hemodialysis patients.}, language = {en} } @article{JanssenHoffmannKannoetal.2020, author = {Janssen, Jan P. and Hoffmann, Jan V. and Kanno, Takayuki and Nose, Naoko and Grunz, Jan-Peter and Onoguchi, Masahisa and Chen, Xinyu and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro}, title = {Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-75696-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230616}, year = {2020}, abstract = {We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available \(^{99m}\)Tc-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with \(^{99m}\)Tc-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with similar to 100 MBq [\(^{99m}\)TcTc-MIBI or similar to 150 MBq [\(^{99m}\)Tc]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1="very poor" to 5="very good". Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5\%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time.}, language = {en} } @article{JovanovicKlassenHeuschmannetal.2020, author = {Jovanovic, Ana and Klassen, Philipp and Heuschmann, Peter and Sommer, Claudia and Roberts, Mark and {\"U}{\c{c}}eyler, Nurcan}, title = {English version of the self-administered Fabry Pain Questionnaire for adult patients}, series = {Orphanet Journal of Rare Diseases}, volume = {15}, journal = {Orphanet Journal of Rare Diseases}, doi = {10.1186/s13023-020-01580-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230298}, year = {2020}, abstract = {Background Pain is an early symptom of Fabry disease (FD) and is characterized by a unique phenotype with mainly episodic acral and triggerable burning pain. Recently, we designed and validated the first pain questionnaire for adult FD patients in an interview and a self-administered version in German: the Wurzburg Fabry Pain Questionnaire (FPQ). We now report the validation of the English version of the self-administered FPQ (enFPQ). Methods After two forward-backward translations of the FPQ by native German and native English speakers, the enFPQ was applied at The Mark Holland Metabolic Unit, Manchester, UK for validation. Consecutive patients with genetically ascertained FD and current or previous FD pain underwent a face-to-face interview using the enFPQ. Two weeks later, patients filled in the self-administered enFPQ at home. The agreement between entries collected by supervised administration and self-administration of the enFPQ was assessed via Gwet's AC1-statistics (AC1) for nominal-scaled scores and intraclass correlation coefficient (ICC) for interval-scaled elements. Results Eighty-three FD patients underwent the face-to-face interview and 54 patients sent back a completed self-administered version of the enFPQ 2 weeks later. We found high agreement with a mean AC1-statistics of 0.725 for 55 items, and very high agreement with a mean ICC of 0.811 for 9 items. Conclusions We provide the validated English version of the FPQ for self-administration in adult FD patients. The enFPQ collects detailed information on the individual FD pain phenotype and thus builds a solid basis for better pain classification and treatment in patients with FD.}, language = {en} } @article{Bauer2020, author = {Bauer, Wolfgang Rudolf}, title = {Impact of Interparticle Interaction on Thermodynamics of Nano-Channel Transport of Two Species}, series = {Entropy}, volume = {22}, journal = {Entropy}, number = {4}, issn = {1099-4300}, doi = {10.3390/e22040376}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203240}, year = {2020}, abstract = {Understanding the function and control of channel transport is of paramount importance for cell physiology and nanotechnology. In particular, if several species are involved, the mechanisms of selectivity, competition, cooperation, pumping, and its modulation need to be understood. What lacks is a rigorous mathematical approach within the framework of stochastic thermodynamics, which explains the impact of interparticle in-channel interactions on the transport properties of the respective species. To achieve this, stochastic channel transport of two species is considered in a model, which different from mean field approaches, explicitly conserves the spatial correlation of the species within the channel by analysis of the stochastic dynamics within a state space, the elements of which are the channel's spatial occupation states. The interparticle interactions determine the stochastic transitions between these states. Local flow and entropy production in this state space reveal the respective particle flows through the channel and the intensity of the Brownian ratchet like rectifying forces, which these species exert mutually on each other, together with its thermodynamic effectiveness and costs. Perfect coupling of transport of the two species is realized by an attractive empty channel and strong repulsive forces between particles of the same species. This confines the state space to a subspace with circular topology, in which the concentration gradients as thermodynamic driving forces act in series, and channel flow of both species becomes equivalent. For opposing concentration gradients, this makes the species with the stronger gradient the driving, positive entropy producing one; the other is driven and produces negative entropy. Gradients equal in magnitude make all flows vanish, and thermodynamic equilibrium occurs. A differential interparticle interaction with less repulsive forces within particles of one species but maintenance of this interaction for the other species adds a bypass path to this circular subspace. On this path, which is not involved in coupling of the two species, a leak flow of the species with less repulsive interparticle interaction emerges, which is directed parallel to its concentration gradient and, hence, produces positive entropy here. Different from the situation with perfect coupling, appropriate strong opposing concentration gradients may simultaneously parallelize the flow of their respective species, which makes each species produce positive entropy. The rectifying potential of the species with the bypass option is diminished. This implies the existence of a gradient of the other species, above which its flow and gradient are parallel for any gradient of the less coupled species. The opposite holds for the less coupled species. Its flow may always be rectified and turned anti-parallel to its gradient by a sufficiently strong opposing gradient of the other one.}, language = {en} } @article{LockUngeheuerBorstetal.2020, author = {Lock, J. F. and Ungeheuer, L. and Borst, P. and Swol, J. and L{\"o}b, S. and Brede, E. M. and R{\"o}der, D. and Lengenfelder, B. and Sauer, K. and Gremer, C. - T.}, title = {Markedly increased risk of postoperative bleeding complications during perioperative bridging anticoagulation in general and visceral surgery}, series = {Perioperative Medicine}, volume = {9}, journal = {Perioperative Medicine}, doi = {10.1186/s13741-020-00170-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230690}, year = {2020}, abstract = {Background Increasing numbers of patients receiving oral anticoagulants are undergoing elective surgery. Low molecular weight heparin (LMWH) is frequently applied as bridging therapy during perioperative interruption of anticoagulation. The aim of this study was to explore the postoperative bleeding risk of patients receiving surgery under bridging anticoagulation. Methods We performed a monocentric retrospective two-arm matched cohort study. Patients that received perioperative bridging anticoagulation were compared to a matched control group with identical surgical procedure, age, and sex. Emergency and vascular operations were excluded. The primary endpoint was the incidence of major postoperative bleeding. Secondary endpoints were minor postoperative bleeding, thromboembolic events, length of stay, and in-hospital mortality. Multivariate analysis explored risk factors of major postoperative bleeding. Results A total of 263 patients in each study arm were analyzed. The patient cohort included the entire field of general and visceral surgery including a large proportion of major oncological resections. Bridging anticoagulation increased the postoperative incidence of major bleeding events (8\% vs. 1\%; p < 0.001) as well as minor bleeding events (14\% vs. 5\%; p < 0.001). Thromboembolic events were equally rare in both groups (1\% vs. 2\%; p = 0.45). No effect on mortality was observed (1.5\% vs. 1.9\%). Independent risk factors of major postoperative bleeding were full-therapeutic dose of LMWH, renal insufficiency, and the procedure-specific bleeding risk. Conclusion Perioperative bridging anticoagulation, especially full-therapeutic dose LMWH, markedly increases the risk of postoperative bleeding complications in general and visceral surgery. Surgeons should carefully consider the practice of routine bridging.}, language = {en} }