@article{BeningGenserKelleretal.2023, author = {Bening, C. and Genser, B. and Keller, D. and M{\"u}ller-Altrock, S. and Radakovic, D. and Penov, K. and Hassan, M. and Aleksic, I. and Leyh, R. and Madrahimov, N.}, title = {Impact of estradiol, testosterone and their ratio on left and right auricular myofilament function in male and female patients undergoing coronary artery bypass grafting}, series = {BMC Cardiovascular Disorders}, volume = {23}, journal = {BMC Cardiovascular Disorders}, doi = {10.1186/s12872-023-03582-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357368}, year = {2023}, abstract = {Background The impact of sex hormones on right and left auricular contractile apparatus function is largely unknown. We evaluated the impact of sex hormones on left and right heart contractility at the level of myocardial filaments harvested from left and right auricles during elective coronary artery bypass surgery. Methods 150 patients (132 male; 18 female) were enrolled. Preoperative testosterone and estradiol levels were measured with Immunoassay. Calcium induced force measurements were performed with left- and right auricular myofilaments in a skinned fiber model. Correlation analysis was used for comparison of force values and levels of sex hormones and their ratio. Results Low testosterone was associated with higher top force values in right-sided myofilaments but not in left-sided myofilaments for both sexes (p = 0.000 in males, p = 0.001 in females). Low estradiol levels were associated with higher top force values in right-sided myofilaments (p 0.000) in females and only borderline significantly associated with higher top force values in males (p 0.056). In females, low estradiol levels correlated with higher top force values in left sided myofilaments (p 0.000). In males, higher Estradiol/Testosterone ratio (E/T ratio) was only associated with higher top force values from right auricular myofilaments (p 0.04) In contrast, in females higher E/T ratio was associated with lower right auricular myofilament top force values (p 0.03) and higher top force values in left-sided myofilaments (p 0.000). Conclusions This study shows that patients' comorbidities influence left and right sided contractility and may blur results concerning influence of sex hormones if not eliminated. A sex hormone dependent influence is obvious with different effects on the left and right ventricle. The E/T ratio and its impact on myofilament top force showed divergent results between genders, and may partially explain gender differences in patients with cardiovascular disease.}, language = {en} } @article{SchmidEckertMeixneretal.2023, author = {Schmid, Benedikt and Eckert, Dominik and Meixner, Andreas and Pistner, Paul and Malzahn, Uwe and Berberich, Monika and Happel, Oliver and Meybohm, Patrick and Kranke, Peter}, title = {Conventional versus video-assisted laryngoscopy for perioperative endotracheal intubation (COVALENT) - a randomized, controlled multicenter trial}, series = {BMC Anesthesiology}, volume = {23}, journal = {BMC Anesthesiology}, doi = {10.1186/s12871-023-02083-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357207}, year = {2023}, abstract = {Background Data on the routine use of video-assisted laryngoscopy in peri-operative intubations are rather inconsistent and ambiguous, in part due to small populations and non-uniform outcome measures in past trials. Failed or prolonged intubation procedures are a reason for relevant morbidity and mortality. This study aims to determine whether video-assisted laryngoscopy (with both Macintosh-shaped and hyperangulated blades) is at least equal to the standard method of direct laryngoscopy with respect to the first-pass success rate. Furthermore, validated tools from the field of human factors will be applied to examine within-team communication and task load during this critical medical procedure. Methods In this randomized, controlled, three-armed parallel group design, multi-centre trial, a total of more than 2500 adult patients scheduled for perioperative endotracheal intubation will be randomized. In equally large arms, video-assisted laryngoscopy with a Macintosh-shaped or a hyperangulated blade will be compared to the standard of care (direct laryngoscopy with Macintosh blade). In a pre-defined hierarchical analysis, we will test the primary outcome for non-inferiority first. If this goal should be met, the design and projected statistical power also allow for subsequent testing for superiority of one of the interventions. Various secondary outcomes will account for patient safety considerations as well as human factors interactions within the provider team and will allow for further exploratory data analysis and hypothesis generation. Discussion This randomized controlled trial will provide a solid base of data in a field where reliable evidence is of major clinical importance. With thousands of endotracheal intubations performed every day in operating rooms around the world, every bit of performance improvement translates into increased patient safety and comfort and may eventually prevent significant burden of disease. Therefore, we feel confident that a large trial has the potential to considerably benefit patients and anaesthetists alike. Trial registration ClincalTrials.gov NCT05228288. Protocol version 1.1, November 15, 2021.}, language = {en} } @article{RadakovicPenovLazarusetal.2023, author = {Radakovic, Dejan and Penov, Kiril and Lazarus, Marc and Madrahimov, Nodir and Hamouda, Khaled and Schimmer, Christoph and Leyh, Rainer G. and Bening, Constanze}, title = {The completeness of the left atrial appendage amputation during routine cardiac surgery}, series = {BMC Cardiovascular Disorders}, volume = {23}, journal = {BMC Cardiovascular Disorders}, doi = {10.1186/s12872-023-03330-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357376}, year = {2023}, abstract = {Background Left atrial appendage (LAA) is the origin of most heart thrombi which can lead to stroke or other cerebrovascular event in patients with non-valvular atrial fibrillation (AF). This study aimed to prove safety and low complication rate of surgical LAA amputation using cut and sew technique with control of its effectiveness. Methods 303 patients who have undergone selective LAA amputation were enrolled in the study in a period from 10/17 to 08/20. The LAA amputation was performed concomitant to routine cardiac surgery on cardiopulmonary bypass with cardiac arrest with or without previous history of AF. The operative and clinical data were evaluated. Extent of LAA amputation was examined intraoperatively by transoesophageal echocardiography (TEE). Six months in follow up, the patients were controlled regarding clinical status and episodes of strokes. Results Average age of study population was 69.9 ± 19.2 and 81.9\% of patients were male. In only three patients was residual stump after LAA amputation larger than 1 cm with average stump size 0.28 ± 0.34 cm. 3 patients (1\%) developed postoperative bleeding. Postoperatively 77 (25.4\%) patients developed postoperative AF (POAF), of which 29 (9.6\%) still had AF at discharge. On 6 months follow up only 5 patients had NYHA class III and 1 NYHA class IV. Seven patients reported with leg oedema and no patient experienced any cerebrovascular event in early postoperative follow up. Conclusion LAA amputation can be performed safely and completely leaving minimal to no LAA residual stump.}, language = {en} } @article{LisowskiHartrampfHasenaueretal.2023, author = {Lisowski, Dominik and Hartrampf, Philipp E. and Hasenauer, Natalie and Nickl, Vera and Monoranu, Camelia-Maria and Tamihardja, J{\"o}rg}, title = {Complete loss of E-cadherin expression in a rare case of metastatic malignant meningioma: a case report}, series = {BMC Neurology}, volume = {23}, journal = {BMC Neurology}, doi = {10.1186/s12883-023-03450-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357996}, year = {2023}, abstract = {Background Hematogenous tumor spread of malignant meningiomas occurs very rarely but is associated with very poor prognosis. Case presentation We report an unusual case of a patient with a malignant meningioma who developed multiple metastases in bones, lungs and liver after initial complete resection of the primary tumor. After partial hepatic resection, specimens were histologically analyzed, and a complete loss of E-cadherin adhesion molecules was found. No oncogenic target mutations were found. The patient received a combination of conventional radiotherapy and peptide receptor radionuclide therapy (PRRT). Due to aggressive tumor behavior and rapid spread of metastases, the patient deceased after initiation of treatment. Conclusions E-cadherin downregulation is associated with a higher probability of tumor invasion and distant metastasis formation in malignant meningioma. Up to now, the efficacy of systemic therapy, including PRRT, is very limited in malignant meningioma patients.}, language = {en} } @article{ZeinerSchroederMetzneretal.2023, author = {Zeiner, Carsten and Schr{\"o}der, Malte and Metzner, Selina and Herrmann, Johannes and Notz, Quirin and Hottenrott, Sebastian and R{\"o}der, Daniel and Meybohm, Patrick and Lepper, Philipp M. and Lotz, Christopher}, title = {High-dose methylprednisolone pulse therapy during refractory COVID-19 acute respiratory distress syndrome: a retrospective observational study}, series = {BMC Pulmonary Medicine}, volume = {23}, journal = {BMC Pulmonary Medicine}, doi = {10.1186/s12890-023-02664-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357231}, year = {2023}, abstract = {Background Current COVID-19 guidelines recommend the early use of systemic corticoids for COVID-19 acute respiratory distress syndrome (ARDS). It remains unknown if high-dose methylprednisolone pulse therapy (MPT) ameliorates refractory COVID-19 ARDS after many days of mechanical ventilation or rapid deterioration with or without extracorporeal membrane oxygenation (ECMO). Methods This is a retrospective observational study. Consecutive patients with COVID-19 ARDS treated with a parenteral high-dose methylprednisolone pulse therapy at the intensive care units (ICU) of two University Hospitals between January 1st 2021 and November 30st 2022 were included. Clinical data collection was at ICU admission, start of MPT, 3-, 10- and 14-days post MPT. Results Thirty-seven patients (mean age 55 ± 12 years) were included in the study. MPT started at a mean of 17 ± 12 days after mechanical ventilation. Nineteen patients (54\%) received ECMO support when commencing MPT. Mean paO2/FiO2 significantly improved 3- (p = 0.034) and 10 days (p = 0.0313) post MPT. The same applied to the necessary FiO2 10 days after MPT (p = 0.0240). There were no serious infectious complications. Twenty-four patients (65\%) survived to ICU discharge, including 13 out of 20 (65\%) needing ECMO support. Conclusions Late administration of high-dose MPT in a critical subset of refractory COVID-19 ARDS patients improved respiratory function and was associated with a higher-than-expected survival of 65\%. These data suggest that high-dose MPT may be a viable salvage therapy in refractory COVID-19 ARDS.}, language = {en} } @article{McNeillRadtkeNieberleretal.2023, author = {McNeill, Rhiannon V. and Radtke, Franziska and Nieberler, Matthias and Koreny, Carolin and Chiocchetti, Andreas G. and Kittel-Schneider, Sarah}, title = {Generation of four human induced pluripotent stem cells derived from ADHD patients carrying different genotypes for the risk SNP rs1397547 in the ADHD-associated gene ADGRL3}, series = {Stem Cell Research}, volume = {67}, journal = {Stem Cell Research}, doi = {10.1016/j.scr.2023.103016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350099}, year = {2023}, abstract = {Single nucleotide polymorphisms (SNPs) in the ADGRL3 gene have been significantly associated with the development of ADHD, the aetiology of which remains poorly understood. The rs1397547 SNP has additionally been associated with significantly altered ADGRL3 transcription. We therefore generated iPSCs from two wild type ADHD patients, and two ADHD patients heterozygous for the risk SNP. With this resource we aim to facilitate further investigation into the complex and heterogenous pathology of ADHD. Furthermore, we demonstrate the feasibility of using magnetic activated cell sorting to allow the unbiased selection of fully reprogrammed iPSCs.}, language = {en} } @article{MeiserMohammadiVogeletal.2023, author = {Meiser, Elisabeth and Mohammadi, Reza and Vogel, Nicolas and Holcman, David and Fenz, Susanne F.}, title = {Experiments in micro-patterned model membranes support the narrow escape theory}, series = {Communications Physics}, volume = {6}, journal = {Communications Physics}, doi = {10.1038/s42005-023-01443-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358121}, year = {2023}, abstract = {The narrow escape theory (NET) predicts the escape time distribution of Brownian particles confined to a domain with reflecting borders except for one small window. Applications include molecular activation events in cell biology and biophysics. Specifically, the mean first passage time τ can be analytically calculated from the size of the domain, the escape window, and the diffusion coefficient of the particles. In this study, we systematically tested the NET in a disc by variation of the escape opening. Our model system consisted of micro-patterned lipid bilayers. For the measurement of τ, we imaged diffusing fluorescently-labeled lipids using single-molecule fluorescence microscopy. We overcame the lifetime limitation of fluorescent probes by re-scaling the measured time with the fraction of escaped particles. Experiments were complemented by matching stochastic numerical simulations. To conclude, we confirmed the NET prediction in vitro and in silico for the disc geometry in the limit of small escape openings, and we provide a straightforward solution to determine τ from incomplete experimental traces.}, language = {en} } @article{MunawarZhouPrommersbergeretal.2023, author = {Munawar, Umair and Zhou, Xiang and Prommersberger, Sabrina and Nerreter, Silvia and Vogt, Cornelia and Steinhardt, Maximilian J. and Truger, Marietta and Mersi, Julia and Teufel, Eva and Han, Seungbin and Haertle, Larissa and Banholzer, Nicole and Eiring, Patrick and Danhof, Sophia and Navarro-Aguadero, Miguel Angel and Fernandez-Martin, Adrian and Ortiz-Ruiz, Alejandra and Barrio, Santiago and Gallardo, Miguel and Valeri, Antonio and Castellano, Eva and Raab, Peter and Rudert, Maximilian and Haferlach, Claudia and Sauer, Markus and Hudecek, Michael and Martinez-Lopez, J. and Waldschmidt, Johannes and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, K. Martin}, title = {Impaired FADD/BID signaling mediates cross-resistance to immunotherapy in Multiple Myeloma}, series = {Communications Biology}, volume = {6}, journal = {Communications Biology}, doi = {10.1038/s42003-023-05683-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357609}, year = {2023}, abstract = {The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has been reported to mediate resistance to CART in acute lymphoblastic leukemia, this mechanism yet remains to be elucidated in context of novel immunotherapies for MM. Here, we describe impaired death receptor signaling as a novel mechanism of resistance to T-cell mediated immunotherapies in MM. This resistance seems exclusive to novel immunotherapies while sensitivity to conventional anti-tumor therapies being preserved in vitro. As a proof of concept, we present a confirmatory clinical case indicating that the FADD/BID axis is required for meaningful responses to novel immunotherapies thus we report impaired death receptor signaling as a novel resistance mechanism to T-cell mediated immunotherapy in MM.}, language = {en} } @article{DoehlerRoederSchlesingeretal.2023, author = {D{\"o}hler, Ida and R{\"o}der, Daniel and Schlesinger, Tobias and Nassen, Christian Alexander and Germer, Christoph-Thomas and Wiegering, Armin and Lock, Johan Friso}, title = {Risk-adjusted perioperative bridging anticoagulation reduces bleeding complications without increasing thromboembolic events in general and visceral surgery}, series = {BMC Anesthesiology}, volume = {23}, journal = {BMC Anesthesiology}, doi = {10.1186/s12871-023-02017-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357305}, year = {2023}, abstract = {Background Perioperative bridging of oral anticoagulation increases the risk of bleeding complications after elective general and visceral surgery. The aim of this study was to explore, whether an individual risk-adjusted bridging regimen can reduce bleeding events, while still protecting against thromboembolic events. Methods We performed a quality improvement study comparing bridging parameters and postoperative outcomes before (period 1) and after implementation (period 2) of a new risk-adjusted bridging regimen. The primary endpoint of the study was overall incidence of postoperative bleeding complications during 30 days postoperatively. Secondary endpoints were major postoperative bleeding, minor bleeding, thromboembolic events, postoperative red blood cell transfusion, perioperative length-of-stay (LOS) and in-hospital mortality. Results A total of 263 patients during period 1 and 271 patients during period 2 were compared. The included elective operations covered the entire field of general and visceral surgery. The overall incidence of bleeding complications declined from 22.1\% during period 1 to 10.3\% in period 2 (p < 0.001). This reduction affected both major as well as minor bleeding events (8.4\% vs. 4.1\%; p = 0.039; 13.7\% vs. 6.3\%; p = 0.004). The incidence of thromboembolic events remained low (0.8\% vs. 1.1\%). No changes in mortality or length-of-stay were observed. Conclusion It is important to balance the individual thromboembolic and bleeding risks in perioperative bridging management. The risk adjusted bridging regimen reduces bleeding events in general and visceral surgery while the risk of thromboembolism remains comparably low.}, language = {en} } @article{ReuterHaufImdahletal.2023, author = {Reuter, Christian and Hauf, Laura and Imdahl, Fabian and Sen, Rituparno and Vafadarnejad, Ehsan and Fey, Philipp and Finger, Tamara and Jones, Nicola G. and Walles, Heike and Barquist, Lars and Saliba, Antoine-Emmanuel and Groeber-Becker, Florian and Engstler, Markus}, title = {Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-43437-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358142}, year = {2023}, abstract = {Transmission of Trypanosoma brucei by tsetse flies involves the deposition of the cell cycle-arrested metacyclic life cycle stage into mammalian skin at the site of the fly's bite. We introduce an advanced human skin equivalent and use tsetse flies to naturally infect the skin with trypanosomes. We detail the chronological order of the parasites' development in the skin by single-cell RNA sequencing and find a rapid activation of metacyclic trypanosomes and differentiation to proliferative parasites. Here we show that after the establishment of a proliferative population, the parasites enter a reversible quiescent state characterized by slow replication and a strongly reduced metabolism. We term these quiescent trypanosomes skin tissue forms, a parasite population that may play an important role in maintaining the infection over long time periods and in asymptomatic infected individuals.}, language = {en} }