@article{HerrmannHerrmannPasslicketal.2022, author = {Herrmann, Anna and Herrmann, Matthias and Passlick, Bernward and Herth, Felix and Herrmann, Johannes}, title = {Cycling-induced recurrent spontaneous pneumomediastinum and pneumopericardium in a young female patient}, series = {Clinical Case Reports}, volume = {10}, journal = {Clinical Case Reports}, number = {3}, doi = {10.1002/ccr3.5587}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276465}, year = {2022}, abstract = {We present an exceptional case of recurrent cycling-induced spontaneous pneumomediastinum and pneumopericardium in a female patient without any trauma. Radiological and endoscopic examinations were carried out to exclude other differential diagnoses. Decision for in-hospital observation and conservative treatment was made. No symptoms were reported 12 months after return to sports activity.}, language = {en} } @article{SchwaabBjarnasonWehrensMengetal.2021, author = {Schwaab, Bernhard and Bjarnason-Wehrens, Birna and Meng, Karin and Albus, Christian and Salzwedel, Annett and Schmid, Jean-Paul and Benzer, Werner and Metz, Matthes and Jensen, Katrin and Rauch, Bernhard and B{\"o}nner, Gerd and Brzoska, Patrick and Buhr-Schinner, Heike and Charrier, Albrecht and Cordes, Carsten and D{\"o}rr, Gesine and Eichler, Sarah and Exner, Anne-Kathrin and Fromm, Bernd and Gielen, Stephan and Glatz, Johannes and Gohlke, Helmut and Grilli, Maurizio and Gysan, Detlef and H{\"a}rtel, Ursula and Hahmann, Harry and Herrmann-Lingen, Christoph and Karger, Gabriele and Karoff, Marthin and Kiwus, Ulrich and Knoglinger, Ernst and Krusch, Christian-Wolfgang and Langheim, Eike and Mann, Johannes and Max, Regina and Metzendorf, Maria-Inti and Nebel, Roland and Niebauer, Josef and Predel, Hans-Georg and Preßler, Axel and Razum, Oliver and Reiss, Nils and Saure, Daniel and von Schacky, Clemens and Sch{\"u}tt, Morten and Schultz, Konrad and Skoda, Eva-Maria and Steube, Diethard and Streibelt, Marco and St{\"u}ttgen, Martin and St{\"u}ttgen, Michaela and Teufel, Martin and Tschanz, Hansueli and V{\"o}ller, Heinz and Vogel, Heiner and Westphal, Ronja}, title = {Cardiac rehabilitation in German speaking countries of Europe — evidence-based guidelines from Germany, Austria and Switzerland LLKardReha-DACH — part 2}, series = {Journal of Clinical Medicine}, volume = {10}, journal = {Journal of Clinical Medicine}, number = {14}, issn = {2077-0383}, doi = {10.3390/jcm10143071}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242645}, year = {2021}, abstract = {Background: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients' groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. Methods: Generation of evidence and search of literature have been described in part 1. Results: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for "distress management" and "lifestyle changes". PE is able to increase patients' knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients' groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. Conclusions: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively.}, language = {en} } @article{NotzHeylandLeeetal.2023, author = {Notz, Quirin and Heyland, Daren K. and Lee, Zheng-Yii and Menger, Johannes and Herrmann, Johannes and Chillon, Thilo S. and Fremes, Stephen and Mohammadi, Siamak and Elke, Gunnar and Mazer, C. David and Hill, Aileen and Velten, Markus and Ott, Sascha and Kleine-Brueggeney, Maren and Meybohm, Patrick and Schomburg, Lutz and Stoppe, Christian}, title = {Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial}, series = {Intensive Care Medicine Experimental}, volume = {11}, journal = {Intensive Care Medicine Experimental}, doi = {10.1186/s40635-023-00574-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357196}, year = {2023}, abstract = {Background Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment. Methods Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity. Results Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes. Conclusions The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients.}, language = {en} } @article{HerrmannWiederLassmannetal.2014, author = {Herrmann, Ken and Wieder, Hinrich A. and Lassmann, Michael and Allen-Auerbach, Martin S. and Czernin, Johannes}, title = {Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters}, doi = {10.4329/wjr.v6.i7.480}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113014}, year = {2014}, abstract = {Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer. Different radionuclides that emit β-rays such as 153Samarium and 89Strontium and achieve palliation are commercially available. In contrast to β-emitters, 223Radium as a α-emitter has a short path-length. The advantage of the α-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms. Due to the limited range of the α-particles the bone surface to red bone marrow dose ratio is also lower for 223Radium which is expressed in a lower myelotoxicity. The α emitter 223Radium dichloride is the first radiopharmaceutical that significantly prolongs life in castrate resistant prostate cancer patients with wide-spread bone metastatic disease. In a phase III, randomized, double-blind, placebo-controlled study 921 patients with castration-resistant prostate cancer and bone metastases were randomly assigned. The analysis confirmed the 223Radium survival benefit compared to the placebo (median, 14.9 mo vs 11.3 mo; P < 0.001). In addition, the treatment results in pain palliation and thus, improved quality of life and a delay of skeletal related events. At the same time the toxicity profile of 223Radium was favourable. Since May 2013, 223Radium dichloride (Xofigo®) is approved by the US Food and Drug Administration. Core tip: The incidence rate of prostate cancer worldwide is high. Ninety percent of patients dying of prostate cancer have bone metastases with varying symptoms which are significantly impairing their quality of life. 223Radium is the first therapeutic that results in a survival benefit for patients with bone metastatic, castrate resistant prostate cancer. 223Radium was also associated with low myelosuppression rates and fewer adverse events.This article provides an overview of the pre-clinical and clinical trials with 223Radium.}, language = {en} } @phdthesis{Herrmann2019, author = {Herrmann, Johannes Bernd}, title = {Rolle des Komplement C5a-Rezeptors 1 in der Pathophysiologie der Meningokokken-Sepsis}, doi = {10.25972/OPUS-18453}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184533}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Das bekapselte, Gram-negative, diplokokkenf{\"o}rmige Bakterium Neisseria meningitidis (Nme) ist ein asymptomatischer Kommensale des oberen Nasenrachenraums im Men-schen. Gerade bei Kindern ist es dem humanspezifischen Pathogen in seltenen F{\"a}llen m{\"o}glich, in den Blutstrom einzuwandern und lebensbedrohliche Krankheitsbilder wie Meningoenzephalitis und Sepsis auszul{\"o}sen, welche als „Invasive Meningokokkener-krankung" (IMD) zusammengefasst werden. J{\"a}hrlich ereignen sich weltweit bis zu 1,2 Mio F{\"a}lle von IMD, welche aufgrund des fulminanten Verlaufs und der hohen Letalit{\"a}t gef{\"u}rchtet sind. In der Bek{\"a}mpfung der Nme-Sepsis ist das humane Komplementsystem von entscheidender Bedeutung. Vor diesem Hintergrund ist die protektive Rolle des lytischen (Membranangriffskomplex MAK) und opsonisierenden Arms (Opsonine iC3b und C1q) der Komplementkaskade gut dokumentiert. Dagegen ist der Beitrag des in-flammatorischen Arms (Anaphylatoxine C3a und C5a) in der Nme-Sepsis bisher unklar. Aus diesem Grunde wurde mit dieser Arbeit die Rolle des inflammatorischen Arms an-hand des Komplement C5a-Rezeptors 1 (C5aR1) in der Pathophysiologie der Nme-Sepsis am Mausmodell untersucht. Nach Etablierung des murinen, intraperitonealen In-fektionsmodells konnte ein sch{\"a}dlicher Effekt des C5aR1 in der Nme-Sepsis beobachtet werden. Aus der Abwesenheit des C5aR1 resultierte eine h{\"o}here {\"U}berlebensrate, ein besserer klinischer Zustand, eine niedrigere Bakteri{\"a}mie und niedrigere Konzentrationen der pro-inflammatorischen Mediatoren IL-6, CXCL-1 und TNF-α. Im Hinblick auf den zellul{\"a}ren Pathomechanismus sprechen Ergebnisse dieser Arbeit daf{\"u}r, dass der C5aR1 prim{\"a}r eine gesteigerte Freisetzung inflammatorischer Mediatoren durch verschiedene Zellpopulationen triggert (Zytokinsturm), wodurch sekund{\"a}r Zellparalyse, steigende Bakteri{\"a}mie und h{\"o}here Letalit{\"a}t bedingt sind. Durch Depletionsversuche und Immun-fluoreszenzf{\"a}rbungen konnte, unabh{\"a}ngig vom C5aR1, eine allgemein protektive Rolle von neutrophilen Granulozyten und Monozyten/Makrophagen in der Nme-Sepsis beo-bachtet werden. Dar{\"u}ber hinaus pr{\"a}sentierte sich der zyklische C5aR1-Antagonist PMX205 als erfolgsversprechende Therapieoption, um Parameter einer murinen Nme-Sepsis zu verbessern. Weitere Untersuchungen sind n{\"o}tig, um die Wirksamkeit dieser Substanz in der humanen Nme-Sepsis zu erforschen. Zudem k{\"o}nnte das murine, intrape-ritoneale Infektionsmodell zur Kl{\"a}rung der Rolle des C5aR2 in der Nme-Sepsis genutzt werden.}, subject = {Komplement C5a}, language = {de} } @article{HerrmannMuenstermannStrobeletal.2018, author = {Herrmann, Johannes and Muenstermann, Marcel and Strobel, Lea and Schubert-Unkmeir, Alexandra and Woodruff, Trent M. and Gray-Owen, Scott D. and Klos, Andreas and Johswich, Kay O.}, title = {Complement C5a receptor 1 exacerbates the pathophysiology of N. meningitidis sepsis and is a potential target for disease treatment}, series = {mBio}, volume = {9}, journal = {mBio}, number = {1}, doi = {10.1128/mBio.01755-17}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175792}, pages = {e01755-17}, year = {2018}, abstract = {Sepsis caused by Neisseria meningitidis (meningococcus) is a rapidly progressing, life-threatening disease. Because its initial symptoms are rather unspecific, medical attention is often sought too late, i.e., when the systemic inflammatory response is already unleashed. This in turn limits the success of antibiotic treatment. The complement system is generally accepted as the most important innate immune determinant against invasive meningococcal disease since it protects the host through the bactericidal membrane attack complex. However, complement activation concomitantly liberates the C5a peptide, and it remains unclear whether this potent anaphylatoxin contributes to protection and/or drives the rapidly progressing immunopathogenesis associated with meningococcal disease. Here, we dissected the specific contribution of C5a receptor 1 (C5aR1), the canonical receptor for C5a, using a mouse model of meningococcal sepsis. Mice lacking C3 or C5 displayed susceptibility that was enhanced by >1,000-fold or 100-fold, respectively, consistent with the contribution of these components to protection. In clear contrast, C5ar1\(^{-/-}\) mice resisted invasive meningococcal infection and cleared N. meningitidis more rapidly than wild-type (WT) animals. This favorable outcome stemmed from an ameliorated inflammatory cytokine response to N. meningitidis in C5ar1\(^{-/-}\) mice in both in vivo and ex vivo whole-blood infections. In addition, inhibition of C5aR1 signaling without interference with the complement bactericidal activity reduced the inflammatory response also in human whole blood. Enticingly, pharmacologic C5aR1 blockade enhanced mouse survival and lowered meningococcal burden even when the treatment was administered after sepsis induction. Together, our findings demonstrate that C5aR1 drives the pathophysiology associated with meningococcal sepsis and provides a promising target for adjunctive therapy. Importance: The devastating consequences of N. meningitidis sepsis arise due to the rapidly arising and self-propagating inflammatory response that mobilizes antibacterial defenses but also drives the immunopathology associated with meningococcemia. The complement cascade provides innate broad-spectrum protection against infection by directly damaging the envelope of pathogenic microbes through the membrane attack complex and triggers an inflammatory response via the C5a peptide and its receptor C5aR1 aimed at mobilizing cellular effectors of immunity. Here, we consider the potential of separating the bactericidal activities of the complement cascade from its immune activating function to improve outcome of N. meningitidis sepsis. Our findings demonstrate that the specific genetic or pharmacological disruption of C5aR1 rapidly ameliorates disease by suppressing the pathogenic inflammatory response and, surprisingly, allows faster clearance of the bacterial infection. This outcome provides a clear demonstration of the therapeutic benefit of the use of C5aR1-specific inhibitors to improve the outcome of invasive meningococcal disease.}, language = {en} } @article{HerrmannAdamNotzetal.2020, author = {Herrmann, Johannes and Adam, Elisabeth Hannah and Notz, Quirin and Helmer, Philipp and Sonntagbauer, Michael and Ungemach-Papenberg, Peter and Sanns, Andreas and Zausig, York and Steinfeldt, Thorsten and Torje, Iuliu and Schmid, Benedikt and Schlesinger, Tobias and Rolfes, Caroline and Reyher, Christian and Kredel, Markus and Stumpner, Jan and Brack, Alexander and Wurmb, Thomas and Gill-Schuster, Daniel and Kranke, Peter and Weismann, Dirk and Klinker, Hartwig and Heuschmann, Peter and R{\"u}cker, Viktoria and Frantz, Stefan and Ertl, Georg and Muellenbach, Ralf Michael and Mutlak, Haitham and Meybohm, Patrick and Zacharowski, Kai and Lotz, Christopher}, title = {COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study}, series = {Frontiers in Medicine}, volume = {7}, journal = {Frontiers in Medicine}, issn = {2296-858X}, doi = {10.3389/fmed.2020.599533}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219834}, year = {2020}, abstract = {Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0\%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5\%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3\%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.}, language = {en} } @article{HerrmannNotzSchlesingeretal.2021, author = {Herrmann, Johannes and Notz, Quirin and Schlesinger, Tobias and Stumpner, Jan and Kredel, Markus and Sitter, Magdalena and Schmid, Benedikt and Kranke, Peter and Schulze, Harald and Meybohm, Patrick and Lotz, Christopher}, title = {Point of care diagnostic of hypercoagulability and platelet function in COVID-19 induced acute respiratory distress syndrome: a retrospective observational study}, series = {Thrombosis Journal}, volume = {19}, journal = {Thrombosis Journal}, number = {1}, doi = {10.1186/s12959-021-00293-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260739}, year = {2021}, abstract = {Background Coronavirus disease 2019 (COVID-19) associated coagulopathy (CAC) leads to thromboembolic events in a high number of critically ill COVID-19 patients. However, specific diagnostic or therapeutic algorithms for CAC have not been established. In the current study, we analyzed coagulation abnormalities with point-of-care testing (POCT) and their relation to hemostatic complications in patients suffering from COVID-19 induced Acute Respiratory Distress Syndrome (ARDS). Our hypothesis was that specific diagnostic patterns can be identified in patients with COVID-19 induced ARDS at risk of thromboembolic complications utilizing POCT. Methods This is a single-center, retrospective observational study. Longitudinal data from 247 rotational thromboelastometries (Rotem®) and 165 impedance aggregometries (Multiplate®) were analysed in 18 patients consecutively admitted to the ICU with a COVID-19 induced ARDS between March 12th to June 30th, 2020. Results Median age was 61 years (IQR: 51-69). Median PaO2/FiO2 on admission was 122 mmHg (IQR: 87-189), indicating moderate to severe ARDS. Any form of hemostatic complication occurred in 78 \% of the patients with deep vein/arm thrombosis in 39 \%, pulmonary embolism in 22 \%, and major bleeding in 17 \%. In Rotem® elevated A10 and maximum clot firmness (MCF) indicated higher clot strength. The delta between EXTEM A10 minus FIBTEM A10 (ΔA10) > 30 mm, depicting the sole platelet-part of clot firmness, was associated with a higher risk of thromboembolic events (OD: 3.7; 95 \%CI 1.3-10.3; p = 0.02). Multiplate® aggregometry showed hypoactive platelet function. There was no correlation between single Rotem® and Multiplate® parameters at intensive care unit (ICU) admission and thromboembolic or bleeding complications. Conclusions Rotem® and Multiplate® results indicate hypercoagulability and hypoactive platelet dysfunction in COVID-19 induced ARDS but were all in all poorly related to hemostatic complications..}, language = {en} } @article{NotzLotzHerrmannetal.2021, author = {Notz, Quirin and Lotz, Christopher and Herrmann, Johannes and Vogt, Marius and Schlesinger, Tobias and Kredel, Markus and Muellges, Wolfgang and Weismann, Dirk and Westermaier, Thomas and Meybohm, Patrick and Kranke, Peter}, title = {Severe neurological complications in critically ill COVID‑19 patients}, series = {Journal of Neurology}, journal = {Journal of Neurology}, issn = {0340-5354}, doi = {10.1007/s00415-020-10152-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232429}, pages = {1576-1579}, year = {2021}, abstract = {No abstract available.}, language = {en} } @article{SchlesingerWeissbrichWedekinketal.2020, author = {Schlesinger, Tobias and Weißbrich, Benedikt and Wedekink, Florian and Notz, Quirin and Herrmann, Johannes and Krone, Manuel and Sitter, Magdalena and Schmid, Benedikt and Kredel, Markus and Stumpner, Jan and D{\"o}lken, Lars and Wischhusen, J{\"o}rg and Kranke, Peter and Meybohm, Patrick and Lotz, Christpher}, title = {Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study}, series = {PLoS One}, volume = {15, 2020}, journal = {PLoS One}, number = {11}, doi = {10.1371/journal.pone.0242917}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231348}, year = {2020}, abstract = {Background The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). Methods This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay. Results Most patients (91\%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30\%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100\% of the cases, oropharyngeal swabs only in 77\%. Blood samples were positive in 26\% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009). Conclusions COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity.}, language = {en} }