G Marx

RWTH Aachen University, Aachen, North Rhine-Westphalia, Germany

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Publications (211)701.82 Total impact

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    ABSTRACT: Cardiac surgery encompasses various stimuli that trigger pro-inflammatory mediators, reactive oxygen species and mobilization of leucocytes. The aim of this study was to evaluate the effect of xenon on the inflammatory response during cardiac surgery. This randomized trial enrolled 30 patients who underwent elective on-pump coronary-artery bypass grafting in balanced anaesthesia of either xenon or sevoflurane. For this secondary analysis, blood samples were drawn prior to the operation, intra-operatively and on the first post-operative day to measure the pro- and anti-inflammatory cytokines interleukin-6 (IL-6), interleukin-8/C-X-C motif ligand 8 (IL-8/CXCL8), and interleukin-10 (IL-10). Chemokines such as C-X-C motif ligand 12/ stromal cell-derived factor-1α (CXCL12/SDF-1α) and macrophage migration inhibitory factor (MIF) were measured to characterize xenon’s perioperative inflammatory profile and its impact on migration of peripheral blood mononuclear cells (PBMC). Xenon enhanced the postoperative increase of IL-6 compared to sevoflurane (Xenon: 90.7 versus sevoflurane: 33.7 pg/ml; p = 0.035) and attenuated the increase of IL-10 (Xenon: 127.9 versus sevoflurane: 548.3 pg/ml; p = 0.028). Both groups demonstrated a comparable intraoperative increase of oxidative stress (intra-OP: p = 0.29; post-OP: p = 0.65). While both groups showed an intraoperative increase of the cardioprotective mediators MIF and CXCL12/SDF-1α, only MIF levels decreased in the xenon group on the first postoperative day (50.0 ng/ml compared to 23.3 ng/ml; p = 0.012), whereas it remained elevated after sevoflurane anaesthesia (58.3 ng/ml to 53.6 ng/ml). Effects of patients’ serum on chemotactic migration of peripheral mononuclear blood cells taken from healthy volunteers indicated a tendency towards enhanced migration after sevoflurane anaesthesia (p = 0.07). Compared to sevoflurane, balanced xenon anaesthesia triggers pro-inflammatory effects and suppresses the anti-inflammatory response in cardiac surgery patients even though the clinical significance remains unknown. Trial registration This clinical trial was approved by the European Medicines Agency (EudraCT-number: 2010-023942-63) and at ClinicalTrials.gov (NCT01285271; first received: January 24, 2011).
    Critical care (London, England) 12/2015; 19(1-1):365. DOI:10.1186/s13054-015-1082-7 · 4.48 Impact Factor
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    ABSTRACT: Background In this observational study near infrared spectroscopy (NIRS) was evaluated as a non-invasive monitor of impaired tissue oxygenation (StO2) after cardiac surgery. StO2, cardiac output, mixed venous oxygen saturation and mean arterial pressure were compared with lactate clearance as established measure for sufficient tissue perfusion and oxygen metabolism. Methods Forty patients after cardiac surgery (24 aortocoronary bypass grafting, 5 heart valve, 3 ascending aorta and 8 combined procedures) were monitored until postoperative day 1 with NIRS of the thenar muscle (InSpectra™ StO2-monitor, Hutchinson Technology), a pulmonary-artery catheter and intermittent blood gas analyses for the assessment of lactate clearance. Results StO2 was reduced 4 h after surgery (75 ± 6 %), but recovered at day 1 (84 ± 5 %), while lactate concentration remained increased. Using uni- and multivariate regression analysis, minimum StO2 (r = 0.46, p <0.01) and cardiac index (r = 0.40, p <0.05) correlated with lactate clearance at day 1, while minimum mixed venous saturation and mean arterial pressure did not. In a receiver-operating characteristics (ROC) analysis, minimum StO2 (with a threshold of 75 %) predicted a lactate clearance <10 % at day 1 with an area under the ROC-curve of 0.83, a sensitivity of 78 % and a specificity of 88 %. In the subgroup with StO2 <75 %, troponin and creatine kinase MB were significantly increased at day 1. Conclusions StO2 below 75 % in the first hours after surgery was a better early indicator of persistent impaired lactate clearance at day 1 than cardiac index, mixed venous oxygen saturation or mean arterial pressure.
    BMC Anesthesiology 12/2015; 15(1). DOI:10.1186/s12871-015-0140-7 · 1.38 Impact Factor
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    ABSTRACT: Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains from their proteoglycans. Thereby, heparanase liberates highly potent circulating heparan sulfate-fragments (HS-fragments) and triggers the fatal and excessive inflammatory response in sepsis. As a potential anti-inflammatory agent for sepsis therapy, peptide 19-2.5 belongs to the class of synthetic anti-lipopolysaccharide peptides; however, its activity is not restricted to Gram-negative bacterial infection. We hypothesized that peptide 19-2.5 interacts with heparanase and/or HS, thereby reducing the levels of circulating HS-fragments in murine and human sepsis. Our data indicate that the treatment of septic mice with peptide 19-2.5 compared to untreated control animals lowers levels of plasma heparanase and circulating HS-fragments and reduces heparanase activity. Additionally, mRNA levels of heparanase in heart, liver, lung, kidney and spleen are downregulated in septic mice treated with peptide 19-2.5 compared to untreated control animals. In humans, plasma heparanase level and activity are elevated in septic shock. The ex vivo addition of peptide 19-2.5 to plasma of septic shock patients decreases heparanase activity but not heparanase level. Isothermal titration calorimetry revealed a strong exothermic reaction between peptide 19-2.5 and heparanase and HS-fragments. However, a saturation character has been identified only in the peptide 19-2.5 and HS interaction. In conclusion, the findings of our current study indicate that peptide 19-2.5 interacts with heparanase, which is elevated in murine and human sepsis and consecutively attenuates the generation of circulating HS-fragments in systemic inflammation. Thus, peptide 19-2.5 seems to be a potential anti-inflammatory agent in sepsis.
    PLoS ONE 11/2015; 10(11):e0143583. DOI:10.1371/journal.pone.0143583 · 3.23 Impact Factor
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    ABSTRACT: To secure the functionality of activated macrophages in the innate immune response, efficient life span control is required. Recognition of bacterial lipopolysaccharides (LPS) by toll-like receptor 4 (TLR4) induces downstream signaling pathways, which merge to induce the expression of cytokine genes and anti-apoptotic genes. MicroRNAs (miRNAs) have emerged as important inflammatory response modulators, but information about their functional impact on apoptosis is scarce. To identify miRNAs differentially expressed in response to LPS, cDNA libraries from untreated and LPS-activated murine macrophages were analyzed by deep sequencing and regulated miRNA expression was verified by Northern blotting and qPCR. Employing TargetScan™ we identified CASPASE-3 (CASP-3) mRNA that encodes a key player in apoptosis as potential target of LPS-induced miR-155. LPS-dependent primary macrophage activation revealed TLR4-mediated enhancement of miR-155 expression and CASP-3 mRNA reduction. Endogenous CASP-3 and cleaved CASP-3 protein declined in LPS-activated macrophages. Accumulation of miR-155 and CASP-3 mRNA in miRNA-induced silencing complexes (miRISC) was demonstrated by ARGONAUTE 2 (AGO2) immunoprecipitation. Importantly, specific antagomir transfection effectively reduced mature miR-155 and resulted in significantly elevated CASP-3 mRNA levels in activated macrophages. In vitro translation assays demonstrated that the target site in the CASP-3 mRNA 3'UTR mediates miR-155-dependent Luciferase reporter mRNA destabilization. Strikingly, Annexin V staining of macrophages transfected with antagomir-155 and stimulated with LPS prior to staurosporine (SSP) treatment implied that LPS-induced miR-155 prevents apoptosis through CASP-3 mRNA down-regulation. In conclusion, we report that miR-155-mediated CASP-3 mRNA destabilization in LPS-activated RAW 264.7 macrophages suppresses apoptosis, as a prerequisite to maintain their crucial function in inflammation.
    RNA Biology 11/2015; DOI:10.1080/15476286.2015.1109768 · 4.97 Impact Factor
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    ABSTRACT: The heart is one of the most frequently affected organs in sepsis. Recent studies focused on lipopolysaccharide induced mitochondrial dysfunction, however myocardial dysfunction is not restricted to Gram-negative bacterial sepsis. The purpose of this study was to investigate circulating heparan sulfate (HS) as an endogenous danger associated molecule causing cardiac mitochondrial dysfunction in sepsis. We used an in vitro model with native sera (SsP) and sera eliminated from HS (HS-free), both of septic shock patients, to stimulate murine cardiomyocytes. As determined by extracellular flux analyzing, SsP increased basal mitochondrial respiration, but reduced maximum mitochondrial respiration, compared to unstimulated cells (p < 0.0001 and p < 0.0001, respectively). Cells stimulated with HS-free serum revealed unaltered basal and maximum mitochondrial respiration, compared to unstimulated cells (p = 0.1174 and p = 0.8992, respectively). Cellular ATP-level were decreased in SsP-stimulated cells but unaltered in cells stimulated with HS-free serum compared to unstimulated cells (p < 0.0001 and p = 0.1593, respectively). Live-cell imaging revealed an increased production of mitochondrial reactive oxygen species in cells stimulated with SsP compared to cells stimulated with HS-free serum (p < 0.0001). Expression of peroxisome proliferator-activated receptors (PPARα and PPARγ) and their co-activators PGC-1α, which regulate mitochondrial function were studied using PCR. Cells stimulated with SsP showed downregulated PPARs and PGC-1α mRNA-levels compared to HS-free serum (p = 0.0082, p = 0.0128 and p = 0.0185 respectively). Blocking Toll-like receptor 4 revealed an inhibition of HS-dependent downregulation of PPARs and PGC-1α (all p < 0.0001). In conclusion, circulating HS in serum of septic shock patients cause cardiac mitochondrial dysfunction, suggesting HS may be targets of therapeutics in septic cardiomyopathy.
    Shock (Augusta, Ga.) 11/2015; DOI:10.1097/SHK.0000000000000462 · 3.05 Impact Factor

  • Der Anaesthesist 10/2015; DOI:10.1007/s00101-015-0105-8 · 0.76 Impact Factor

  • ains · Anästhesiologie · Intensivmedizin 10/2015; 50(10):589-590. DOI:10.1055/s-0041-107533 · 0.44 Impact Factor

  • Clinical Infectious Diseases 10/2015; DOI:10.1093/cid/civ887 · 8.89 Impact Factor
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    10/2015; 3(Suppl 1):A516. DOI:10.1186/2197-425X-3-S1-A516
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    10/2015; 3(Suppl 1):A302. DOI:10.1186/2197-425X-3-S1-A302

  • 10/2015; 3(Suppl 1):A256. DOI:10.1186/2197-425X-3-S1-A256

  • European Respiratory Journal 09/2015; 46(suppl 59):PA2166. DOI:10.1183/13993003.congress-2015.PA2166 · 7.64 Impact Factor
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    Gernot Marx · Rainer Beckers ·

    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 08/2015; 58(10). DOI:10.1007/s00103-015-2232-4 · 1.42 Impact Factor
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    ABSTRACT: The demographic challenge of the ageing society is associated with increasing comorbidity. On the other hand, there will be an ageing workforce in medicine, resulting in an imbalance between the demand and supply of medical care in the near future. In rural areas in particular, this imbalance is already present today. Based on three best practice projects carried out by our telemedical center in Aachen, including emergency medicine, intensive care medicine, and the rehabilitation planning of geriatric trauma care, some experience and the potential of the intersectoral provision of care, supported by telemedicine, are demonstrated. Telemedicine is the provision of medical services over a geographical distance by using tele-communication and data transfer. It has been proven to ensure a constant quality of health care. Telemedical support enables shared expertise independent of time and space, and allows efficient allocation of resources. A review of international experience supports this notion.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 08/2015; DOI:10.1007/s00103-015-2224-4 · 1.42 Impact Factor
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    ABSTRACT: In view of demographic changes over the past few decades, the average age of trauma patients is progressively increasing. We therefore aimed to summarize the specific characteristics of geriatric trauma and to identify potential fields for further research to improve the care of elderly trauma patients. Review of the literature. Due to the diverse risk factors (e.g., pre-existing conditions, limited physiological reserve), geriatric patients are prone to developing severe complications, even after less severe trauma. Yet, age is not considered as the only predictor of worse outcomes, and it should not be considered the only criterion for limiting care in those patients. It is crucial that age-specific treatment guidelines are developed to optimize the outcomes for senior trauma patients. Based on the current literature, these guidelines should emphasize the importance of field triage directly to a trauma center, along with the activation of the trauma team. Furthermore, early intensive monitoring, aggressive resuscitation, and time of surgical intervention are of upmost importance to reduce mortality. The impact of several factors [age, premedical conditions (PMC), decreased physiological reserves, and impaired immune function] on the post-traumatic course of elderly trauma patients needs to be clarified in future experimental and clinical studies for the early identification of geriatric high-risk patients and for the development of age-adapted therapeutic strategies.
    European Journal of Trauma and Emergency Surgery 08/2015; DOI:10.1007/s00068-015-0557-1 · 0.35 Impact Factor
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    ABSTRACT: Patients and medical staff are exposed to high noise levels in ICUs, which may have a negative impact on their health. Due to the diversity of noise sources present, including the operating noise of medical devices, staff conversations and the unwrapping of disposables, noise profiles are varied. Psychoacoustics deals with the analysis of sound, focusing on its effects on physiological perception and stress. The aim of our study was to examine and to classify noise and its psychoacoustic properties in different locations in our ICU at different times. The impact of noise on subjective parameters and stress-related physiological data was also assessed with and without interventional methods. A randomised, controlled, single-blinded clinical trial SETTING: University Hospital, from November 2010 to May 2011. One hundred and forty-four patients in the ICU. In the first part, multidisciplinary psychoacoustic measurement was performed on the patients in our ICU. In the subsequent clinical trial, patients were equipped with effective earplugs, less effective earplugs and no earplugs. Thereafter, active noise cancellation headphones with or without sound masking were employed on a third patient population. Cortisol and α-amylase in saliva, skin conductance measures, vital signs, psychoacoustic analyses and two standardised questionnaires [State-Trait Anxiety Inventory (STAI) and Hospital Anxiety and Depression Scale (HADS)] were assessed. In the first part, the mean ± standard deviation (SD) subjective loudness was 9.2 ± 4.0 sone. Although absolute sound pressure level and loudness were lower during the night, the number of loud events increased significantly. Skin conductance in the earplug groups was significantly reduced in comparison to that in the control population but not the active noise reduction groups. Nevertheless, noise reduction was found to be comfortable for most patients. Noise in the ICU is of high clinical relevance. Diverse noise reduction methods, such as earplugs and active noise cancellation, are available. The avoidance of unnecessary noise, however, should be the primary focus. German Clinical Trials Register (DRKS00000534).
    European Journal of Anaesthesiology 07/2015; DOI:10.1097/EJA.0000000000000313 · 2.94 Impact Factor
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    ABSTRACT: Myocardial dysfunction in sepsis has been linked to inflammation caused by pathogen-associated molecular patterns (PAMPs) as well as by host danger-associated molecular patterns (DAMPs). These include soluble heparan sulfate (HS), which triggers the devastating consequences of the pro-inflammatory cascades in severe sepsis and septic shock. Thus, there is increasing interest in the development of anti-infective agents, with effectiveness against both PAMPs and DAMPs. We hypothesized that a synthetic antimicrobial peptide (peptide 19-2.5) inhibits inflammatory response in murine cardiomyocytes (HL-1 cells) stimulated with PAMPs, DAMPs or serum from patients with septic shock by reduction and/or neutralization of soluble HS. In the current study, our data indicate that the treatment with peptide 19-2.5 decreases the inflammatory response in HL-1 cells stimulated with either PAMPs or DAMPs. Furthermore, our work shows that soluble HS in serum from patients with Gram-negative or Gram-positive septic shock induces a strong pro-inflammatory response in HL-1 cells, which can be effectively blocked by peptide 19-2.5. Based on these findings, peptide 19-2.5 is a novel anti-inflammatory agent interacting with both PAMPs and DAMPs, suggesting peptide 19-2.5 may have the potential for further development as a broad-spectrum anti-inflammatory agent in sepsis-induced myocardial inflammation and dysfunction.
    PLoS ONE 05/2015; 10(5):e0127584. DOI:10.1371/journal.pone.0127584 · 3.23 Impact Factor
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    ABSTRACT: Zinc is crucial for immune function. In addition, the redistribution of zinc and other nutrients due to infection is an integral part of the host immune response to limit availability to pathogens. However, the major zinc binding protein albumin is down regulated during the acute phase response, implicating a decrease in zinc binding capacity. A prospective animal study with eight female German landrace pigs was conducted to investigate alterations in zinc binding capacity, total serum zinc and free zinc levels in the initial phase of sepsis. Sepsis was induced by instillation of autologous feces via midline laparotomy. Total serum zinc declined significantly after 1 h (10.89 ± 0.42 µM vs. 7.67 ± 0.41 µM, p < 0.001), total serum copper and iron reached a significant reduction at 4 h. Urinary excretion of zinc declined in line with total serum zinc. In comparison to total serum zinc, free zinc levels declined to a lesser, though significant, extent. Zinc binding capacity of serum decreased over time, whereby free zinc levels after addition of zinc correlated negatively with total serum protein and albumin levels. In addition IL-6 and TNF-α concentrations were measured and increased significantly 2 h after induction of sepsis. Hence, total serum zinc was the first marker of inflammation in our experiment, and might therefore be a promising biomarker for the early diagnosis of sepsis. Furthermore the observation of a substantially different serum free zinc homeostasis during sepsis provides valuable information for a potential therapeutic zinc supplementation, which has to take buffering capacity by serum proteins into account.
    Biology of Metals 05/2015; 28(4). DOI:10.1007/s10534-015-9858-4 · 2.50 Impact Factor
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    ABSTRACT: Background: Intensive care medicine (ICM) is a key discipline in medicine, but nonetheless only few topics are inte grated in undergraduate curricula. Students are easily overwhelmed by the complexity of ICM. Because of an unpredictable workload and regular intermissions, student tutoring by physicians in ICM clerkships is very difficult and can hardly be structured. The previous knowledge of ICM seems to be less detailed than in other medical disciplines. Peer-assisted learning (PAL) is a well-known and reliable concept of learning and teaching. During ICM clerkships PAL might be a useful approach to give students the opportunity of receiving continuous tutoring. Furthermore, it offers students the chance to become more acquainted with the theory and practice in intensive care medicine. Methods: During their practical clerkships the medical students in their fourth and fifth year spend a period of four weeks with clerkships in the fields of anaesthesiology, intensive care medicine and emergency medicine. The PAL concept was implemented and evaluated as a part of this scheme. Learning objectives were defined by experienced medical teachers. Student-tutors were selected as peer tutors and trained by physicians concerning skills and knowledge about the procedures in an intensive care unit (ICU). Furthermore, they were taught basic didactical principles. All participants were assigned to two groups, i.e. a PAL group, who had peer tutors and a control group (KG) without PAL. Instead of PAL, the members of the control group took part an additional seminar led by an experienced ICU physician. For evaluation purposes, questionnaires regarding knowledge acceptance and course rating were developed. Results: A structured PAL concept was developed for clinical clerkship in ICM. During the last academic year, 221 students participated in this clerkship. Data from 142 students (61% female, 39% male: age mean 24.1, SD±2.1) were collected. The control/reference group consisted of 83, the PAL group of 59 participants. Independent of their respective group affiliations, both groups rated the clerkship as positive. There were no differences in knowledge, familiarity with ward procedures and course rating. More than 90% of the medical teachers evaluated the PAL concept as beneficial, whereas 60% considered teaching without peers to interfere with patient care and daily work. PAL was rated as positive in terms of the students' learning achievement. The majority (96%) of medical teachers advocated for the continuation of PAL during ICU clerkship. Conclusion: The implementation of PAL in ICU clerkship works well, and there is a high acceptance among both students and medical teachers. The students' view was more critical than that of the teachers. Nonetheless, the PAL concept is a considerable opportunity to implement clerkship in an ICU. The PAL concept also preserves/saves the resources of a professional teacher on ward. On the whole, the PAL concepts received a good evaluation by the participating students and medical teachers. The transferability of this study to other areas of university teaching seems possible and should be examined in future studies.
    Anasthesiologie und Intensivmedizin 05/2015; 56(5):206-215. · 1.09 Impact Factor
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Publication Stats

2k Citations
701.82 Total Impact Points


  • 2009-2015
    • RWTH Aachen University
      • • Klinik für Operative Intensivmedizin und Intermediate Care
      • • Department of Anaesthesiology
      Aachen, North Rhine-Westphalia, Germany
  • 2008-2014
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 1996-2012
    • Hannover Medical School
      • Clinic for Anaesthesiology and Intensive Care Medicine
      Hanover, Lower Saxony, Germany
  • 2004-2011
    • Friedrich-Schiller-University Jena
      • • Clinic of General, Visceral and Vascular Surgery
      • • Department of Anaesthesiology and Intensive Care Medicine
      Jena, Thuringia, Germany
  • 2006-2009
    • Universitätsklinikum Jena
      • Klinik für Anästhesiologie und Intensivmedizin
      Jena, Thuringia, Germany
  • 2001-2005
    • Royal Liverpool and Broadgreen University Hospitals NHS Trust
      • Department of Anaesthesia
      Liverpool, England, United Kingdom
  • 2001-2004
    • University of Liverpool
      • Department of Clinical Sciences
      Liverpool, England, United Kingdom