TY - JOUR A1 - Herrmann, Johannes A1 - Lotz, Christopher A1 - Karagiannidis, Christian A1 - Weber-Carstens, Steffen A1 - Kluge, Stefan A1 - Putensen, Christian A1 - Wehrfritz, Andreas A1 - Schmidt, Karsten A1 - Ellerkmann, Richard K. A1 - Oswald, Daniel A1 - Lotz, Gösta A1 - Zotzmann, Viviane A1 - Moerer, Onnen A1 - Kühn, Christian A1 - Kochanek, Matthias A1 - Muellenbach, Ralf A1 - Gaertner, Matthias A1 - Fichtner, Falk A1 - Brettner, Florian A1 - Findeisen, Michael A1 - Heim, Markus A1 - Lahmer, Tobias A1 - Rosenow, Felix A1 - Haake, Nils A1 - Lepper, Philipp M. A1 - Rosenberger, Peter A1 - Braune, Stephan A1 - Kohls, Mirjam A1 - Heuschmann, Peter A1 - Meybohm, Patrick T1 - Key characteristics impacting survival of COVID-19 extracorporeal membrane oxygenation JF - Critical Care N2 - Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO\(_{2}\)/FiO\(_{2}\) ratio prior to ECMO was 72 mmHg (IQR: 58–99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41–0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28–1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival. KW - Covid-19 KW - extracorporeal membrane oxygenation (ECMO) KW - intensive care unit Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299686 VL - 26 IS - 1 ER - TY - JOUR A1 - Biehl, Stefanie C. A1 - Merz, Christian J. A1 - Dresler, Thomas A1 - Heupel, Julia A1 - Reichert, Susanne A1 - Jacob, Christian P. A1 - Deckert, Jürgen A1 - Herrmann, Martin J. T1 - Increase or Decrease of fMRI Activity in Adult Attention Deficit/ Hyperactivity Disorder: Does It Depend on Task Difficulty? JF - International Journal of Neuropsychopharmacology N2 - Background: Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap. Methods: Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients. Results: There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients. Conclusions: Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes. KW - working memory KW - clinical trial KW - child memory KW - short-term methylphenidate brain KW - methylphenidate KW - adult attention deficit/hyperactivity disorder KW - fMRI KW - functional magnetic resonance imaging Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147551 VL - 19 IS - 10 ER - TY - JOUR A1 - Colvill, Emma A1 - Booth, Jeremy A1 - Nill, Simeon A1 - Fast, Martin A1 - Bedford, James A1 - Oelfke, Uwe A1 - Nakamura, Mitsuhiro A1 - Poulsen, Per A1 - Worm, Esben A1 - Hansen, Rune A1 - Ravkilde, Thomas A1 - Rydhög, Jonas Scherman A1 - Pommer, Tobias A1 - af Rosenschold, Per Munck A1 - Lang, Stephanie A1 - Guckenberger, Matthias A1 - Groh, Christian A1 - Herrmann, Christian A1 - Verellen, Dirk A1 - Poels, Kenneth A1 - Wang, Lei A1 - Hadsell, Michael A1 - Sothmann, Thilo A1 - Blanck, Oliver A1 - Keall, Paul T1 - A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: a multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking JF - Radiotherapy and Oncology N2 - Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for gamma-tests recorded. Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm gamma-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm gamma-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm gamma-fail rate of <3% for all systems with adaptation for lung and prostate. Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods. KW - Robotic tracking KW - Gimbaled tracking KW - MLC tracking KW - Couch tracking KW - Organ motion Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189605 VL - 119 IS - 1 ER - TY - JOUR A1 - Schwaab, Bernhard A1 - Bjarnason-Wehrens, Birna A1 - Meng, Karin A1 - Albus, Christian A1 - Salzwedel, Annett A1 - Schmid, Jean-Paul A1 - Benzer, Werner A1 - Metz, Matthes A1 - Jensen, Katrin A1 - Rauch, Bernhard A1 - Bönner, Gerd A1 - Brzoska, Patrick A1 - Buhr-Schinner, Heike A1 - Charrier, Albrecht A1 - Cordes, Carsten A1 - Dörr, Gesine A1 - Eichler, Sarah A1 - Exner, Anne-Kathrin A1 - Fromm, Bernd A1 - Gielen, Stephan A1 - Glatz, Johannes A1 - Gohlke, Helmut A1 - Grilli, Maurizio A1 - Gysan, Detlef A1 - Härtel, Ursula A1 - Hahmann, Harry A1 - Herrmann-Lingen, Christoph A1 - Karger, Gabriele A1 - Karoff, Marthin A1 - Kiwus, Ulrich A1 - Knoglinger, Ernst A1 - Krusch, Christian-Wolfgang A1 - Langheim, Eike A1 - Mann, Johannes A1 - Max, Regina A1 - Metzendorf, Maria-Inti A1 - Nebel, Roland A1 - Niebauer, Josef A1 - Predel, Hans-Georg A1 - Preßler, Axel A1 - Razum, Oliver A1 - Reiss, Nils A1 - Saure, Daniel A1 - von Schacky, Clemens A1 - Schütt, Morten A1 - Schultz, Konrad A1 - Skoda, Eva-Maria A1 - Steube, Diethard A1 - Streibelt, Marco A1 - Stüttgen, Martin A1 - Stüttgen, Michaela A1 - Teufel, Martin A1 - Tschanz, Hansueli A1 - Völler, Heinz A1 - Vogel, Heiner A1 - Westphal, Ronja T1 - Cardiac rehabilitation in German speaking countries of Europe — evidence-based guidelines from Germany, Austria and Switzerland LLKardReha-DACH — part 2 JF - Journal of Clinical Medicine N2 - 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. KW - cardiac rehabilitation KW - scientific guidelines KW - secondary prevention KW - physical activity KW - exercise training KW - psychological interventions KW - education KW - gender KW - frailty KW - migration KW - old patients KW - young patients KW - tele-medicine KW - home-based-rehabilitation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242645 SN - 2077-0383 VL - 10 IS - 14 ER - TY - JOUR A1 - Bluemel, Christina A1 - Linke, Fraenze A1 - Herrmann, Ken A1 - Simunovic, Iva A1 - Eiber, Matthias A1 - Kestler, Christian A1 - Buck, Andreas K. A1 - Schirbel, Andreas A1 - Bley, Thorsten A. A1 - Wester, Hans-Juergen A1 - Vergho, Daniel A1 - Becker, Axel T1 - Impact of \(^{68}\)Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy JF - EJNMMI Research N2 - Background Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning. Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity. Results Suspicious lesions were detected in 24/45 (53.3 %) patients. In 62.5 % of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 %) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 %) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 %) within a mean follow-up of 8.12 ± 5.23 months. Conclusions \(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 % of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT. KW - prostate cancer KW - salvage radiotherapy KW - PSMA KW - PET/CT KW - recurrence Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147798 VL - 6 IS - 78 ER - TY - JOUR A1 - Kleinschnitz, Christoph A1 - Grund, Henrike A1 - Wingler, Kirstin A1 - Armitage, Melanie E. A1 - Jones, Emma A1 - Mittal, Manish A1 - Barit, David A1 - Schwarz, Tobias A1 - Geis, Christian A1 - Kraft, Peter A1 - Barthel, Konstanze A1 - Schuhmann, Michael K. A1 - Herrmann, Alexander M. A1 - Meuth, Sven G. A1 - Stoll, Guido A1 - Meurer, Sabine A1 - Schrewe, Anja A1 - Becker, Lore A1 - Gailus-Durner, Valerie A1 - Fuchs, Helmut A1 - Klopstock, Thomas A1 - de Angelis, Martin Hrabe A1 - Jandeleit-Dahm, Karin A1 - Shah, Ajay M. A1 - Weissmann, Norbert A1 - Schmidt, Harald H. H. W. T1 - Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration N2 - Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox42/2) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox42/2 mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy. KW - Schlaganfall Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68416 ER - TY - JOUR A1 - Herrmann, Ken A1 - Buck, Andreas K. A1 - Schuster, Tibor A1 - Abbrederis, Kathrin A1 - Blümel, Christina A1 - Santi, Ivan A1 - Rudelius, Martina A1 - Wester, Hans-Jürgen A1 - Peschel, Christian A1 - Schwaiger, Markus A1 - Dechow, Tobias A1 - Keller, Ulrich T1 - Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL JF - Oncotarget N2 - Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure. KW - [18F]Fluorodeoxythymidine KW - FLT-PET KW - positron emission tomography KW - DLBCL KW - lymphoma Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120659 SN - 1949-2553 VL - 5 IS - 12 ER - TY - JOUR A1 - Ladwig, Karl-Heinz A1 - Lederbogen, Florian A1 - Albus, Christian A1 - Angermann, Christiane A1 - Borggrefe, Martin A1 - Fischer, Denise A1 - Fritzsche, Kurt A1 - Haass, Markus A1 - Jordan, Jochen A1 - Jünger, Jana A1 - Kindermann, Ingrid A1 - Köllner, Volker A1 - Kuhn, Bernhard A1 - Scherer, Martin A1 - Seyfarth, Melchior A1 - Völler, Heinz A1 - Waller, Christiane A1 - Herrmann-Lingen, Christoph T1 - Position paper on the importance of psychosocial factors in cardiology: Update 2013 T1 - Positionspapier zur Bedeutung psychosozialer Faktoren in der Kardiologie: Update 2013 JF - GMS German Medical Science N2 - Background: The rapid progress of psychosomatic research in cardiology and also the increasing impact of psychosocial issues in the clinical daily routine have prompted the Clinical Commission of the German Heart Society (DGK) to agree to an update of the first state of the art paper on this issue which was originally released in 2008. Methods: The circle of experts was increased, general aspects were implemented and the state of the art was updated. Particular emphasis was dedicated to coronary heart diseases (CHD), heart rhythm diseases and heart failure because to date the evidence-based clinical knowledge is most advanced in these particular areas. Differences between men and women and over the life span were considered in the recommendations as were influences of cognitive capability and the interactive and synergistic impact of classical somatic risk factors on the affective comorbidity in heart disease patients. Results: A IA recommendation (recommendation grade I and evidence grade A) was given for the need to consider psychosocial risk factors in the estimation of coronary risks as etiological and prognostic risk factors. Furthermore, for the recommendation to routinely integrate psychosocial patient management into the care of heart surgery patients because in these patients, comorbid affective disorders (e.g. depression, anxiety and post-traumatic stress disorder) are highly prevalent and often have a malignant prognosis. A IB recommendation was given for the treatment of psychosocial risk factors aiming to prevent the onset of CHD, particularly if the psychosocial risk factor is harmful in itself (e.g. depression) or constrains the treatment of the somatic risk factors. Patients with acute and chronic CHD should be offered anti-depressive medication if these patients suffer from medium to severe states of depression and in this case medication with selective reuptake inhibitors should be given. In the long-term course of treatment with implanted cardioverter defibrillators (ICDs) a subjective health technology assessment is warranted. In particular, the likelihood of affective comorbidities and the onset of psychological crises should be carefully considered. Conclusions: The present state of the art paper presents an update of current empirical evidence in psychocardiology. The paper provides evidence-based recommendations for the integration of psychosocial factors into cardiological practice and highlights areas of high priority. The evidence for estimating the efficiency for psychotherapeutic and psychopharmacological interventions has increased substantially since the first release of the policy document but is, however, still weak. There remains an urgent need to establish curricula for physician competence in psychodiagnosis, communication and referral to ensure that current psychocardiac knowledge is translated into the daily routine. N2 - Hintergrund: Die rasche Weiterentwicklung der psychokardiologischen Forschung, aber auch die wachsende Verankerung psychosozialer Fragestellungen im klinischen Alltag haben die Klinische Kommission der DGK bewogen, einer Aktualisierung und Weiterentwicklung des 2008 erstmals publizierten Positionspapiers zur Bedeutung psychosozialer Faktoren in der Kardiologie zuzustimmen. Methoden: Der Kreis der Autoren wurde vergrößert, allgemeine Aspekte eingefügt und das Wissen in allen Abschnitten auf den heutigen Stand gebracht. Schwerpunkte der Empfehlungen sind die koronare Herzerkrankung, Herzrhythmusstörungen und die Herzinsuffizienz, da hier der Stand der empirischen Evidenz und des klinisches Wissens zu psychosozialen Fragestellungen am weitesten entwickelt ist. Berücksichtigt wurden bei den Empfehlungen Besonderheiten von Frauen und Männern, Unterschiede bzgl. der Lebensspanne, Einflüsse auf die kognitive Leistungsfähigkeit und die interaktive synergistische Bedeutung klassischer Risikofaktoren bei affektiver Komorbidität. Ergebnisse: Eine I-A-Empfehlung (Empfehlungsgrad I, Evidenzgrad A) wurde vergeben für die Aufforderung, psychosoziale Risikofaktoren bei der Einschätzung des KHK-Risikos zu berücksichtigen, die als unabhängige ätiologische und prognostische Risikofaktoren für das Auftreten der koronaren Herzerkrankung (KHK) und für Komplikationen im Behandlungsverlauf der KHK bedeutsam sind. Ferner für die Empfehlung, Patienten mit Herzoperationen von einem interdisziplinären Team zu betreuten, in dem die Möglichkeit besteht, auf psychosoziale Aspekte einzugehen, da bei diesen Patienten komorbide psychische Störungen wie Depressivität, Angst und posttraumatische Belastungsstörung häufig und prognostisch ungünstig sind. Eine I-B-Empfehlung wurde vergeben für die Behandlung psychosozialer Risikofaktoren mit dem Ziel einer Primärprävention der KHK, wenn das Risikomerkmal an sich Krankheitswert hat (z. B. Depression) oder die Behandlung klassischer Risikofaktoren erschwert ist. Eine antidepressive Pharmakotherapie soll Patienten nach akutem Koronarsyndrom sowie in der Phase der chronischen KHK angeboten werden, die an einer mindestens mittelschweren rezidivierenden depressiven Störung leiden. Dabei sollen vorzugsweise Substanzen aus der Gruppe der selektiven Serotoninwiederaufnahmehemmer (SSRI) zum Einsatz kommen. Bei der langfristigen ärztlichen Begleitung von ICD-Patienten sollen die psychosozialen Folgen der ICD-Technologie beachtet und insbesondere relevante Affektstörungen sowie Krisen bei ICD-Patienten erkannt und fachgerecht behandelt werden. Schlussfolgerungen: Das Positionspapier formuliert konkrete Anwendungsfelder mit hoher Priorität für die Einbeziehung psychosozialer Faktoren in die kardiologische Praxis, die eine leitlinienkonforme Evidenz aufweisen. Trotz deutlicher Fortschritte seit der Erstveröffentlichung des Positionspapiers existieren weiterhin Forschungsdefizite für die Bewertung der Wirksamkeit psychotherapeutischer und psychopharmakologischer Konzepte bei kardialen Patienten. Curricula für die Vermittlung von (psycho-)diagnostischer, kommunikativer und differenzialdiagnostischer Kompetenz müssen rasch entwickelt werden, um eine Transmission des aktuellen Wissensstands in die Alltagspraxis zu ermöglichen. KW - depression KW - anxiety KW - post-traumatic stress disorder KW - psychotherapy KW - psychopharmacology KW - Depression KW - Psychopharmakologie KW - Psychotherapie KW - posttraumatische Belastungsstörung KW - Angst Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121196 VL - 12 ER - TY - JOUR A1 - Klauke, Benedikt A1 - Winter, Bernward A1 - Gajewska, Agnes A1 - Zwanzger, Peter A1 - Reif, Andreas A1 - Herrmann, Martin J. A1 - Dlugos, Andrea A1 - Warrings, Bodo A1 - Jacob, Christian A1 - Mühlberger, Andreas A1 - Arolt, Volker A1 - Pauli, Paul A1 - Deckert, Jürgen A1 - Domschke, Katharina T1 - Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma JF - PLoS One N2 - The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system - partly conferred by catechol-O-methyltransferase (COMT) gene variation - for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders. KW - COMT VAL(158)MET polymorphism KW - serotonin transporter gene KW - life events KW - community sample KW - acoustic startle KW - prepulse inhibition KW - panic disorder KW - caffeine-induced anxiety KW - fear-potentiated startle KW - posttraumatic-stress-disorder Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132184 VL - 7 IS - 6 ER - TY - JOUR A1 - Graf, Nicolas A1 - Li, Zhoulei A1 - Herrmann, Ken A1 - Weh, Daniel A1 - Aichler, Michaela A1 - Slawska, Jolanta A1 - Walch, Axel A1 - Peschel, Christian A1 - Schwaiger, Markus A1 - Buck, Andreas K. A1 - Dechow, Tobias A1 - Keller, Ulrich T1 - Positron emission tomographic monitoring of dual phosphatidylinositol-3-kinase and mTOR inhibition in anaplastic large cell lymphoma JF - Oncotargets and Therapy N2 - Background: Dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibition offers an attractive therapeutic strategy in anaplastic large cell lymphoma depending on oncogenic nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) signaling. We tested the efficacy of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in two anaplastic large cell lymphoma cell lines in vitro and in vivo and performed an early response evaluation with positron emission tomography (PET) imaging using the standard tracer, 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) and the thymidine analog, 3'-deoxy-3'-[F-18] fluorothymidine (FLT). Methods: The biological effects of BGT226 were determined in vitro in the NPM-ALK positive cell lines SU-DHL-1 and Karpas299 by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, propidium iodide staining, and biochemical analysis of PI3K and mTOR downstream signaling. FDG-PET and FLT-PET were performed in immunodeficient mice bearing either SU-DHL-1 or Karpas299 xenografts at baseline and 7 days after initiation of treatment with BGT226. Lymphomas were removed for immunohistochemical analysis of proliferation and apoptosis to correlate PET findings with in vivo treatment effects. Results: SU-DHL-1 cells showed sensitivity to BGT226 in vitro, with cell cycle arrest in G0/G1 phase and an IC50 in the low nanomolar range, in contrast with Karpas299 cells, which were mainly resistant to BGT226. In vivo, both FDG-PET and FLT-PET discriminated sensitive from resistant lymphoma, as indicated by a significant reduction of tumor-to-background ratios on day 7 in treated SU-DHL-1 lymphoma-bearing animals compared with the control group, but not in animals with Karpas299 xenografts. Imaging results correlated with a marked decrease in the proliferation marker Ki67, and a slight increase in the apoptotic marker, cleaved caspase 3, as revealed by immunostaining of explanted lymphoma tissue. Conclusion: Dual PI3K/mTOR inhibition using BGT226 is effective in ALK-positive anaplastic large cell lymphoma and can be monitored with both FDG-PET and FLT-PET early on in the course of therapy. KW - mammalian target of rapamycin KW - phosphatidylinositol-3-kinase KW - lymphoma KW - early response KW - NVP-BGT226 KW - non-hodgkins-lymphoma KW - signaling pathway KW - FDG-PET KW - in-vivo KW - target KW - tumor KW - imaging proliferation KW - inhibition KW - positron emission tomography Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117915 VL - 7 ER - TY - THES A1 - Herrmann, Christian T1 - Robotic Motion Compensation for Applications in Radiation Oncology T1 - Robotergestützte Bewegungskompensation für Anwendungen in der Radioonkologie N2 - Aufgrund vieler Verbesserungen der Behandlungsmethoden im Laufe der letzten 60 Jahre, erlaubt die Strahlentherapie heutzutage präzise Behandlungen von statischen Tumoren. Jedoch birgt die Bestrahlung von sich bewegenden Tumoren noch große Herausforderungen in sich, da bewegliche Tumore oft den Behandlungsstrahl verlassen. Dabei reduziert sich die Strahlendosis im Tumor während sich diese im umliegenden gesunden Gewebe erhöht. Diese Forschungsarbeit zielt darauf ab, die Grenzen der Strahlentherapie zu erweitern, um präzise Behandlungen von beweglichen Tumoren zu ermöglichen. Der Fokus der Arbeit liegt auf der Erstellung eines Echtzeitsystems zur aktiven Kompensation von Tumorbewegungen durch robotergestützte Methoden. Während Behandlungen befinden sich Patienten auf einer Patientenliege, mit der statische Lagerungsfehler vor Beginn einer Behandlung korrigiert werden. Die in dieser Arbeit verwendete Patientenliege "HexaPOD" ist ein paralleler Manipulator mit sechs Freiheitsgraden, der große Lasten innerhalb eines eingeschränkten Arbeitsbereichs präzise positionieren kann. Obwohl der HexaPOD ursprünglich nicht für dynamische Anwendungen konzipiert wurde, wird dieser für eine dauerhafte Bewegungskompensation eingesetzt, in dem Patienten so bewegt werden, dass Tumore präzise im Zentralstrahl während der Dauer einer gesamten Behandlung verbleiben. Um ein echtzeitfähiges Kompensationssystem auf Basis des HexaPODs zu realisieren, muss eine Reihe an Herausforderungen bewältigt werden. Echtzeitaspekte werden einerseits durch die Verwendung eines harten Echtzeitbetriebssystems abgedeckt, andererseits durch die Messung und Schätzung von Latenzzeiten aller physikalischen Größen im System, z.B. Messungen der Tumor- und Atemposition. Neben der konsistenten und durchgängigen Berücksichtigung von akkuraten Zeitinformation, werden alle software-induzierten Latenzen adaptiv ausgeglichen. Dies erfordert Vorhersagen der Tumorposition in die nahe Zukunft. Zahlreiche Prädiktoren zur Atem- und Tumorpositionsvorhersage werden vorgeschlagen und anhand verschiedenster Metriken evaluiert. Erweiterungen der Prädiktionsalgorithmen werden eingeführt, die sowohl Atem- als auch Tumorpositionsinformationen fusionieren, um Vorhersagen ohne explizites Korrelationsmodell zu ermöglichen. Die Vorhersagen bestimmen den zukünftigen Bewegungspfad des HexaPODs, um Tumorbewegungen zu kompensieren. Dazu werden verschiedene Regler entwickelt, die eine Trajektorienverfolgung mit dem HexaPOD ermöglichen. Auf der Basis von linearer und nicht-linearer dynamischer Modellierung des HexaPODs mit Methoden der Systemidentifikation, wird zunächst ein modellprädiktiver Regler entwickelt. Ein zweiter Regler wird auf Basis einer Annahme über das Arbeitsprinzip des internen Reglers im HexaPOD entworfen. Schließlich wird ein dritter Regler vorgeschlagen, der beide vorhergehenden Regler miteinander kombiniert. Für jeden dieser Regler werden vergleichende Ergebnisse aus Experimenten mit realer Hardware und menschlichen Versuchspersonen präsentiert und diskutiert. Darüber hinaus wird die geeignete Wahl von freien Parametern in den Reglern vorgestellt. Neben einer präzisen Verfolgung der Referenztrajektorie spielt der Patientenkomfort eine entscheidende Rolle für die Akzeptanz des Systems. Es wird gezeigt, dass die Regler glatte Trajektorien realisieren können, um zu garantieren, dass sich Patienten wohl fühlen während ihre Tumorbewegung mit Genauigkeiten im Submillimeterbereich ausgeglichen wird. Gesamtfehler werden im Kompensationssystem analysiert, in dem diese zu Trajektorienverfolgungsfehlern und Prädiktionsfehlern in Beziehung gesetzt werden. Durch Ausnutzung von Eigenschaften verschiedener Prädiktoren wird gezeigt, dass die Startzeit des Systems bis die Verfolgung der Referenztrajektorie erreicht ist, wenige Sekunden beträgt. Dies gilt insbesondere für den Fall eines initial ruhenden HexaPODs und ohne Vorwissen über Tumorbewegungen. Dies zeigt die Eignung des Systems für die sehr kurz fraktionierten Behandlungen von Lungentumoren. Das Tumorkompensationssystem wurde ausschließlich auf Basis von klinischer Standard-Hardware entwickelt, die in vielen Behandlungsräumen zu finden ist. Durch ein einfaches und flexibles Design können Behandlungsräume in kosteneffizienter Weise um Möglichkeiten der Bewegungskompensation ergänzt werden. Darüber hinaus werden aktuelle Behandlungsmethoden wie intensitätsmodulierte Strahlentherapie oder Volumetric Modulated Arc Therapy in keiner Weise eingeschränkt. Aufgrund der Unterstützung verschiedener Kompensationsmodi kann das System auf alle beweglichen Tumore angewendet werden, unabhängig davon ob die Bewegungen vorhersagbar (Lungentumore) oder nicht vorhersagbar (Prostatatumore) sind. Durch Integration von geeigneten Methoden zur Tumorpositionsbestimmung kann das System auf einfache Weise zur Kompensation von anderen Tumoren erweitert werden. N2 - Radiation therapy today, on account of improvements in treatment procedures over the last 60 years, allows precise treatment of static tumors inside the human body. However, irradiation of moving tumors is still a challenging task as moving tumors often leave the treatment beam and the radiation dose delivered to the tumor reduces simultaneously increasing that on healthy tissue. This research work aims to push the frontiers of radiation therapy in order to enable precise treatment of moving tumors with focus on research and development of a unique real-time system enabling active motion compensation through robotic means to compensate tumor motion. During treatment, patients lie on a treatment couch which is normally used for static position corrections of patient set-up errors prior to radiation treatment. The treatment couch used, called HexaPOD, is a parallel manipulator with six degrees of freedom which can precisely position heavy loads inside a small region. Despite the HexaPOD not initially built with dynamics in mind, it is used in this work for sustained motion compensation by moving patients such that tumors stay precisely located at the center of the treatment beam during the complete course of treatment. In order to realize real-time tumor motion compensation by means of the HexaPOD, several challanges need to be addressed. Real-time aspects are covered by the adoption of a hard real-time operation system in combination with measurement and estimation of latencies of all physical quantities in the compensation system such as tumor or breathing position measurements. Accurate timing information is respected consistently in the whole system and all software-induced latencies are adaptively compensated for. This requires knowledge of future tumor positions from predictors. Several predictors for breathing and tumor motion predictions are proposed and evaluated in terms of a variety of different performance metrics. Extensions to prediction algorithms are introduced fusing both breathing and tumor position information to allow for predictions without the need of an explicit correlation model. Predictions determine the future motion path of the HexaPOD in order to compensate for tumor motion. Several control schemes are developed to enable reference tracking for the HexaPOD. Based on linear and non-linear dynamic modelling of the HexaPOD with system identification methods, a first controller is derived in the form of a model predictive controller. A second controller is proposed based on an assumption of the working principle of the HexaPOD's internal controller. Finally, a third controller is derived as combination of the first and second one. For each of these controllers, comparative results with real hardware experiments and humans in the loop as well as choices of free parameters are presented and discussed. Apart from precise tracking, emphasis is placed on patient comfort which is of crucial importance for acceptance of the system. It is demonstrated that smooth trajectories can be realized by the controllers to guarantee that patients feel comfortable while their tumor motion is compensated at sub-millimeter accuracies. Overall errors of the system are analyzed by relating them to tracking and prediction errors. By exploiting the properties of different predictors, it is shown that the startup time until tracking is reached can be reduced to only a few seconds, even in the case of an initially at-rest HexaPOD and with no initial knowledge of tumor motion. This makes the system especially suitable for the relatively short-fractionated treatment sessions for lung tumors. The tumor motion compensation system has been developed solely based on standard clinical hardware, found in most treatment rooms. With a simple and flexible design, existing treatment can be updated in a cost-efficient way to introduce motion compensation capabilities. Simultaneously, the system does not impose any constraints on state-of-the-art treatment types such as intensity modulated radiotherapy or volumetric modulated arc therapy. Supporting different compensation modes, the system can be applied to any moving tumor whether its motion is predictable (lung tumors) or unpredictable (prostate tumors). By integration of adequate tumor position determination methods, the system can be easily extended to other tumors as well. T3 - Forschungsberichte in der Robotik = Research Notes in Robotics - 7 KW - Robotik KW - Bewegungskompensation KW - Regelung KW - Strahlentherapie KW - Vorhersage KW - Tumorbewegung KW - Echzeit KW - Prediction KW - Tumor motion KW - Real-time Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-79045 SN - 978-3-923959-88-4 ER - TY - JOUR A1 - Philipp-Abbrederis, Kathrin A1 - Herrmann, Ken A1 - Knop, Stefan A1 - Schottelius, Margret A1 - Eiber, Matthias A1 - Lückerath, Katharina A1 - Pietschmann, Elke A1 - Habringer, Stefan A1 - Gerngroß, Carlos A1 - Franke, Katharina A1 - Rudelius, Martina A1 - Schirbel, Andreas A1 - Lapa, Constantin A1 - Schwamborn, Kristina A1 - Steidle, Sabine A1 - Hartmann, Elena A1 - Rosenwald, Andreas A1 - Kropf, Saskia A1 - Beer, Ambros J A1 - Peschel, Christian A1 - Einsele, Hermann A1 - Buck, Andreas K A1 - Schwaiger, Markus A1 - Götze, Katharina A1 - Wester, Hans-Jürgen A1 - Keller, Ulrich T1 - In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma JF - EMBO Molecular Medicine N2 - CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases. KW - FDG PET/CT KW - cells KW - CXCR4/SDF-1 KW - CXCR4 KW - multiple myeloma KW - positron emission tomography KW - chemokine receptor KW - in vivo imaging KW - malignancies KW - involvement KW - microenvironment KW - survival KW - cancer KW - autologous transplantation KW - bone disease Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148738 VL - 7 IS - 4 ER - TY - JOUR A1 - Butt, Elke A1 - Stempfle, Katrin A1 - Lister, Lorenz A1 - Wolf, Felix A1 - Kraft, Marcella A1 - Herrmann, Andreas B. A1 - Viciano, Cristina Perpina A1 - Weber, Christian A1 - Hochhaus, Andreas A1 - Ernst, Thomas A1 - Hoffmann, Carsten A1 - Zernecke, Alma A1 - Frietsch, Jochen J. T1 - Phosphorylation-dependent differences in CXCR4-LASP1-AKT1 interaction between breast cancer and chronic myeloid leukemia JF - Cells N2 - The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor 4 (CXCR4), and both proteins play a central role in the modulation of diverse cellular processes, including proliferation and cell survival. While in chronic myeloid leukemia (CML) the CXCR4 is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptor is highly expressed in breast cancer cells, favoring the migratory capacity of these cells. Recently, the LIM and SH3 domain protein 1 (LASP1) has been described as a novel CXCR4 binding partner and as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding of LASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays, pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1 at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally, findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronic myeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment. KW - LASP1 KW - CXCR4 KW - AKT1 KW - CML KW - breast cancer Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200638 SN - 2073-4409 VL - 9 IS - 2 ER - TY - JOUR A1 - Roth, Nicolas A1 - Hacker, Herrmann Heinrich A1 - Heidrich, Lea A1 - Friess, Nicolas A1 - García-Barroas, Enrique A1 - Habel, Jan Christian A1 - Thorn, Simon A1 - Müler, Jörg T1 - Host specificity and species colouration mediate the regional decline of nocturnal moths in central European forests JF - Ecography N2 - The high diversity of insects has limited the volume of long-term community data with a high taxonomic resolution and considerable geographic replications, especially in forests. Therefore, trends and causes of changes are poorly understood. Here we analyse trends in species richness, abundance and biomass of nocturnal macro moths in three quantitative data sets collected over four decades in forests in southern Germany. Two local data sets, one from coppiced oak forests and one from high oak forests included 125K and 48K specimens from 559 and 532 species, respectively. A third regional data set, representing all forest types in the temperate zone of central Europe comprised 735K specimens from 848 species. Generalized additive mixed models revealed temporal declines in species richness (−38%), abundance (−53%) and biomass (−57%) at the regional scale. These were more pronounced in plant host specialists and in dark coloured species. In contrast, the local coppiced oak forests showed an increase, in species richness (+62%), while the high oak forests showed no clear trends. Left and right censoring as well as cross validation confirmed the robustness of the analyses, which led to four conclusions. First, the decline in insects appears in hyper diverse insect groups in forests and affects species richness, abundance and biomass. Second, the pronounced decline in host specialists suggests habitat loss as an important driver of the observed decline. Third, the more severe decline in dark species might be an indication of global warming as a potential driver. Fourth, the trends in coppiced oak forests indicate that maintaining complex and diverse forest ecosystems through active management may be a promising conservation strategy in order to counteract negative trends in biodiversity, alongside rewilding approaches. KW - climate change KW - colour patterns KW - global change KW - Lepidoptera KW - macro moths KW - specialists KW - time series Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258731 VL - 44 IS - 6 ER - TY - JOUR A1 - Herrmann, Johannes A1 - Adam, Elisabeth Hannah A1 - Notz, Quirin A1 - Helmer, Philipp A1 - Sonntagbauer, Michael A1 - Ungemach-Papenberg, Peter A1 - Sanns, Andreas A1 - Zausig, York A1 - Steinfeldt, Thorsten A1 - Torje, Iuliu A1 - Schmid, Benedikt A1 - Schlesinger, Tobias A1 - Rolfes, Caroline A1 - Reyher, Christian A1 - Kredel, Markus A1 - Stumpner, Jan A1 - Brack, Alexander A1 - Wurmb, Thomas A1 - Gill-Schuster, Daniel A1 - Kranke, Peter A1 - Weismann, Dirk A1 - Klinker, Hartwig A1 - Heuschmann, Peter A1 - Rücker, Viktoria A1 - Frantz, Stefan A1 - Ertl, Georg A1 - Muellenbach, Ralf Michael A1 - Mutlak, Haitham A1 - Meybohm, Patrick A1 - Zacharowski, Kai A1 - Lotz, Christopher T1 - COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study JF - Frontiers in Medicine N2 - 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. KW - COVID-19 KW - ARDS (acute respiratory distress syndrome) KW - intensive care medicine KW - pandemia KW - Germany Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219834 SN - 2296-858X VL - 7 ER - TY - JOUR A1 - Notz, Quirin A1 - Herrmann, Johannes A1 - Schlesinger, Tobias A1 - Helmer, Philipp A1 - Sudowe, Stephan A1 - Sun, Qian A1 - Hackler, Julian A1 - Roeder, Daniel A1 - Lotz, Christopher A1 - Meybohm, Patrick A1 - Kranke, Peter A1 - Schomburg, Lutz A1 - Stoppe, Christian T1 - Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS JF - Nutrients N2 - The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r\(_s\) = −0.495), PCT (r\(_s\) = −0.413), IL-6 (r\(_s\) = −0.429), IL-1β (r\(_s\) = −0.440) and IL-10 (r\(_s\) = −0.461). Positive associations were found for CD8\(^+\) T cells (r(_s\) = 0.636), NK cells (r\(_s\) = 0.772), total IgG (r\(_s\) = 0.493) and PaO\(_2\)/FiO\(_2\) ratios (r\(_s\) = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS. KW - acute respiratory distress syndrome KW - selen KW - zinc KW - critical care KW - oxidative stress KW - nutrient supplementation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241112 SN - 2072-6643 VL - 13 IS - 6 ER - TY - JOUR A1 - Lindhoff-Last, Edelgard A1 - Birschmann, Ingvild A1 - Bidenharn, Antonia J. A1 - Kuhn, Joachim A1 - Lindau, Simone A1 - Konstantinides, Stavros A1 - Grottke, Oliver A1 - Nowak-Göttl, Ulrike A1 - Lucks, Jessica A1 - Zydek, Barbara A1 - Heymann, Christian von A1 - Sümnig, Ariane A1 - Beyer-Westendorf, Jan A1 - Schellong, Sebastian A1 - Meybohm, Patrick A1 - Greinacher, Andreas A1 - Herrmann, Eva T1 - Pharmacokinetics of phenprocoumon in emergency situations – results of the prospective observational RADOA-registry (reversal agent use in patients treated with direct oral anticoagulants or vitamin K antagonists registry) JF - Pharmaceuticals N2 - Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings (n = 82) and with urgent surgery (n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22% vs. 4.2% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days. KW - phenprocoumon KW - pharmacokinetics KW - emergency KW - major bleeding KW - urgent surgery KW - INR rebound Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297226 SN - 1424-8247 VL - 15 IS - 11 ER -