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Christoph Lichtenstern,
Marcel Hochreiter,
Verena D Zehnter, Thorsten Brenner,
Stefan Hofer,
Markus Mieth,
Markus W Büchler,
Eike Martin,
Markus A Weigand,
Peter Schemmer,
Cornelius J Busch
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ABSTRACT: Liver transplant recipients are at a significant risk for invasive fungal infections (IFI). This retrospective study evaluated the impact of the pretransplant model for end stage liver disease (MELD) on the incidence of posttransplant IFI in a single centre. From 2004 to 2008, 385 liver transplantations were included, from which 210 transplantations were conducted allocated by Child Turcotte Pugh and 175 were allocated by MELD score. Both groups differed regarding the age of transplant recipients (50.1 ± 10.7 vs. 52.5 ± 9.9, P = 0.036), pretransplant MELD score (16.43 ± 8.33 vs. 18.29 ± 9.05), rate of re-transplantations, duration of surgery, demand in blood transfusions and rates of renal impairments. In the MELD era, higher incidences of IFI (pre-MELD 11.9%, MELD 24.0%, P < 0.05) and Candida infections (9% vs. 18.9%, P < 0.05) were observed. There was no difference in the incidence of probable or possible aspergillosis. Mortality, length of stay in intensive care or hospital, and duration of mechanical ventilation did not differ between the pre-MELD and MELD era. Regardless the date of transplantation, patients with fungi-positive samples showed higher mortality rates than patients without. MELD score was analysed as independent predictors for posttransplant IFI. Higher MELD scores predispose to a more problematic postoperative course and are associated with an increase in fungal infections.
Mycoses 01/2013; · 2.25 Impact Factor
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Thorsten Brenner,
Claudia Rosenhagen,
Holger Brandt,
Felix C F Schmitt,
Gregor E Jung,
Peter Schemmer,
Jan Schmidt,
Markus Mieth,
Thomas Bruckner,
Christoph Lichtenstern,
Eike O Martin,
Markus A Weigand,
Stefan Hofer
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ABSTRACT: Valid prognostic factors for early identification of a complicated course after orthotopic liver transplantation from deceased donors are rare. The aim of this study was to investigate the prognostic value of different cell death biomarkers and inflammatory markers in patients after orthotopic liver transplantation from deceased donors.
In total, 100 patients were evaluated for short-term complications within 10 days after orthotopic liver transplantation from deceased donors. Blood samples were collected before surgery, immediately after the end of the surgical procedure, and 1 day and 3, 5, and 7 days later. Plasma levels of total keratin 18, keratin 18 fragments, interleukin 6, tumor necrosis factor α, and soluble intercellular adhesion molecule 1 were measured.
Total keratin 18 was demonstrated to be favorable in its prognostic value for early identification of a complicated course in comparison to routine markers of liver impairment (e.g., aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase). In contrast, inflammation markers (e.g., interleukin 6, tumor necrosis factor α and soluble intercellular adhesion molecule 1) were unsuitable for predicting early complications after liver transplantation from deceased donors.
For early identification of patients at high risk for complications, the implementation of total keratin 18 measurements in routine diagnostics after orthotopic liver transplantation from deceased donors should be taken into consideration.
Transplantation 06/2012; 94(2):185-91. · 4.00 Impact Factor
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ABSTRACT: Sepsis is relevant due to its high morbidity and mortality. For both sepsis diagnosis and outcome prediction many biomarkers have been described in the literature. Most of these markers are objects of scientific interest rather than being introduced into daily clinical practice. However, due to their unspecific character and their insufficient predictive value for the individual person, research focus is still on new aspects in sepsis-related biomarkers.
Beyond the widely used acute-phase proteins C-reactive protein (CRP) and procalcitonin (PCT), many new molecules have been studied deriving from different organs or cells affected, due to the systemic nature of sepsis. Cytokines, coagulation factors/characteristics, vasoactive hormones, and several others have been recently proved to be relevant in sepsis syndrome and probably useful for outcome prediction. However, single time point measurements may be less predictive than consideration of the time-dependent course of parameters. Clinical decision just based on a biomarker is still not feasible because of the huge inter-individual differences in the inflammatory response.
Many biomarkers display relevant correlation with the clinical outcome of patients with severe sepsis and septic shock. Consideration of their time courses may be more reliable than absolute levels. Clinical decision should not be based only on biomarkers but organ dysfunctions, for example, should also be taken into account.
Current Opinion in Infectious Diseases 03/2012; 25(3):328-36. · 4.93 Impact Factor
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Thorsten Brenner,
Thomas H Fleming,
Claudia Rosenhagen,
Ute Krauser,
Markus Mieth,
Thomas Bruckner,
Eike Martin,
Peter P Nawroth,
Markus A Weigand,
Angelika Bierhaus,
Stefan Hofer
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ABSTRACT: Dysfunctions of the L-arginine (L-arg)/nitric-oxide (NO) pathway are suspected to be important for the pathogenesis of multiple organ dysfunction syndrome (MODS) in septic shock. Therefore plasma concentrations of L-arg and asymmetric dimethylarginine (ADMA) were measured in 60 patients with septic shock, 30 surgical patients and 30 healthy volunteers using enzyme linked immunosorbent assay (ELISA) kits. Plasma samples from patients with septic shock were collected at sepsis onset, and 24 h, 4 d, 7 d, 14 d and 28 d later. Samples from surgical patients were collected prior to surgery, immediately after the end of the surgical procedure as well as 24 h later and from healthy volunteers once. In comparison to healthy volunteers and surgical patients, individuals with septic shock showed significantly increased levels of ADMA, as well as a decrease in the ratio of L-arg and ADMA at all timepoints. In septic patients with an acute liver failure (ALF), plasma levels of ADMA and L-arg were significantly increased in comparison to septic patients with an intact hepatic function. In summary it can be stated, that bioavailability of NO is reduced in septic shock. Moreover, measurements of ADMA and L-arg appear to be early predictors for survival in patients with sepsis-associated ALF.
Mediators of Inflammation 01/2012; 2012:210454. · 3.26 Impact Factor
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Thorsten Brenner,
Claudia Rosenhagen,
Isabelle Hornig,
Karsten Schmidt,
Christoph Lichtenstern,
Markus Mieth,
Thomas Bruckner,
Eike Martin,
Paul Schnitzler,
Stefan Hofer,
Markus A Weigand
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ABSTRACT: Recent investigations provided evidence that herpes simplex virus (HSV-1) and cytomegalovirus (CMV) are reactivated in critically ill individuals. However, at this time, it remains unclear whether these viral infections are of real pathogenetic relevance or represent innocent bystanders.
In total, 60 patients with septic shock were enrolled. Blood samples and tracheal secretion were collected at the time of sepsis diagnosis (T0) as well as 7 d (T1), 14 d (T2), 21 d (T3), and 28 d (T4) later. The following virologic diagnostics were performed: (1) Viral load of herpes simplex virus type1 (HSV-1) and cytomegalovirus (CMV) in blood samples as well as tracheal secretion using polymerase chain reaction (PCR). (2) Detection of CMV-antigen (pp65) in blood samples using immunofluorescence microscopy. Furthermore plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were evaluated using ELISA-kits.
Thirty-one patients (51.7%) were found to be positive for HSV-1, whereas in 16 patients (26.7%) CMV could be identified. Patients with a positive PCR for HSV-1 and/or CMV showed a significantly prolonged length of hospital stay and absolute time of respirator-dependant ventilation. Furthermore, survival curves of patients with a high HSV-1-load (>10E8) in tracheal secretion in comparison with those with a lower HSV-1-load (<10E8) revealed a significantly impaired survival.
Viral superinfections with HSV-1 or CMV can frequently be observed in patients with septic shock, especially in those with increased disease severity and a prolonged need for respirator-dependant ventilation. In patients with a viral superinfection morbidity is increased, whereas differences in mortality seem to be dosage-dependant.
Journal of Surgical Research 11/2011; 176(2):571-82. · 2.25 Impact Factor
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Thorsten Brenner,
Stefan Hofer,
Claudia Rosenhagen,
Jochen Steppan,
Christoph Lichtenstern,
Jürgen Weitz,
Thomas Bruckner,
Ivan K Lukic,
Eike Martin,
Angelika Bierhaus,
Ursula Hoffmann,
Markus A Weigand
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ABSTRACT: Severe sepsis, septic shock, and resulting organ failure appear as the most common cause of death in intensive care medicine. Inflammatory mediators (interleukin-6/IL-6), cell adhesion molecules (intercellular adhesion molecule-1/ICAM-1, vascular cell adhesion molecule-1/VCAM-1), and redox active substances (manganese superoxide dismutase/MnSOD, macrophage migration inhibitory factor/MIF) must be considered to be central hubs in the inflammatory process. However, their exact pathophysiologic function and prognostic value are still poorly understood.
In total, 133 individuals (87 patients with severe sepsis or septic shock, 28 postoperative patients after major abdominal surgery, 18 healthy volunteers) were enrolled in the study. Blood samples from septic patients were collected within 24 h after the time of sepsis diagnosis, and 48 and 120 h later; samples from healthy volunteers were collected once, and samples from postoperative patients once immediately after surgery. In all patients we measured plasma levels of IL-6, sICAM-1, sVCAM-1, MnSOD, and MIF using enzyme linked immunosorbent assay (ELISA) kits.
Healthy volunteers and postoperative patients showed comparable levels of cell adhesion molecules. Furthermore, their redox system was activated in a comparable manner, whereas in postoperative patients IL-6 was significantly elevated. Plasma levels of inflammatory mediators, cell adhesion molecules and redox active substances were significantly elevated in septic patients. In patients with sepsis who had died, plasma levels of MIF and MnSOD were significantly elevated in comparison with survivors.
Our results therefore demonstrate that redox active substances may play an important role in the septic inflammatory response. MIF and MnSOD appear to be early predictors for survival in septic patients.
Journal of Surgical Research 11/2010; 164(1):e163-71. · 2.25 Impact Factor
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ABSTRACT: Metastatic liver resection following cytoreductive chemotherapy is an accepted treatment for oligometastatic tumor diseases. Although pulmonary complications are frequently reported in patients undergoing liver surgery including liver transplantation, life-threatening acute respiratory failures in the absence of aspiration, embolism, transfusion-related acute lung injury (TRALI), pulmonary infection, or an obvious source of systemic sepsis are rare. We performed an extensive clinical review of a patient undergoing metastatic liver resection who had a clinical course compatible to an acute respiratory distress syndrome (ARDS) without an obvious cause except for the surgical procedure and multiple preoperative chemotherapies. We hypothesize that either the surgical procedure mediated by cytokines and tumor necrosis factor or possible toxic effects of oxygen applied during general anesthesia were associated with life-threatening respiratory failure in the patient. Discrete and subclinical inflammated alveoli (probably due to multiple preoperative chemotherapies with substances at potential risk for interstitial pneumonitis as well as chest radiation) might therefore be considered as risk factors.
Anesthesiology Research and Practice 01/2010; 2010.
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ABSTRACT: Background. Redox active substances (e.g., Thioredoxin-1, Macrophage Migration Inhibitory Factor) seem to be central hubs in the septic inflammatory process. Materials and Methods. Blood samples from patients with severe sepsis or septic shock (n = 15) were collected at the time of sepsis diagnosis (t0), and 24 (t24) and 48 (t48) hours later; samples from healthy volunteers (n = 18) were collected once; samples from postoperative patients (n = 28) were taken one time immediately after surgery. In all patients, we measured plasma levels of IL-6, TRX1 and MIF. Results. The plasma levels of MIF and TRX1 were significantly elevated in patients with severe sepsis or septic shock. Furthermore, TRX1 and MIF plasma levels showed a strong correlation (t0: r(sp) = 0.720, ρ = 0.698/t24: r(sp) = 0.771, ρ = 0.949). Conclusions. Proinflammatory/~oxidative and anti-inflammatory/~oxidative agents show a high correlation in order to maintain a redox homeostasis and to avoid the harmful effects of an excessive inflammatory/oxidative response.
Mediators of Inflammation 01/2010; 2010:985614. · 3.26 Impact Factor
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ABSTRACT: Severe sepsis, septic shock, and resulting organ failure represent the most common cause of death in intensive care medicine, with mortality ranging from 40% to 70%. It is still unclear whether necrosis or apoptosis plays the predominant role in severe sepsis. Determining the prevalent mode of cell death would be valuable, as new therapeutic agents (eg, antiapoptotic drugs such as caspase inhibitors) may improve unsatisfactory outcomes in patients with severe sepsis. Furthermore, the prognostic value of newly developed cell death serum biomarkers is of great interest.
In total, 147 patients (101 patients with severe sepsis, 28 postoperative patients after major abdominal surgery, 18 healthy volunteers) were enrolled. Baseline and clinical data were evaluated. Blood samples from patients with severe sepsis were collected at the time of sepsis diagnosis, and 48 and 120 hours later; samples from healthy volunteers were collected once, and from postoperative patients, once immediately after surgery. We measured caspase-cleaved and uncleaved cytokeratin-18 (CK-18, intermediate filament protein) as a marker of cell death, isolated CK-18 fragments as a marker of apoptosis, as well as IL-6, soluble vascular cell adhesion molecule, and soluble intercellular adhesion molecule.
Age and sex of patients with severe sepsis and postoperative patients were comparable, whereas healthy volunteers were significantly younger. In healthy volunteers, the mode of cellular turnover was primarily apoptotic cell death. Postoperative patients showed comparable levels of apoptotic activity, but necrotic cell death was markedly increased, probably due to surgical tissue injury. In contrast, patients with severe sepsis, and especially non-survivors of the septic group showed increased levels of markers for both apoptotic and necrotic cell death. In severe septic patients with liver dysfunction, necrosis is increased relative to severe septic patients with intact hepatic function. For severe septic patients with liver dysfunction, a cut-off value for caspase-cleaved and uncleaved cytokeratin-18 could be calculated, in order to identify patients at high risk for death due to severe sepsis.
The measurement of caspase-cleaved and uncleaved cytokeratin-18 appears to be an early predictor for survival in severe septic patients with hepatic dysfunction. Furthermore, the loss of parenchymal cells due to necrosis may be the primary mode of cell death in these patients. This may limit possible therapeutic options.
Critical care (London, England) 07/2009; 13(3):R93. · 4.61 Impact Factor
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ABSTRACT: Recent evidence suggests that the endothelial glycocalix plays an important role in lethal outcomes following sepsis. We therefore tested if the endothelial glycocalix is shed in patients with sepsis compared with patients after major abdominal surgery and healthy volunteers.
A total of 150 individuals were tested for levels of inflammatory markers (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], interleukin-6 [IL-6]) and glycocalix markers (syndecan-1, heparan sulfate). Three groups consisted of patients with severe sepsis or septic shock, patients after major abdominal surgery without systemic inflammatory response syndrome, and healthy volunteers. Blood was drawn, at the time of diagnosis or surgery, and 6, 24, and 48h later. We correlated these markers to each other and to clinically used inflammation markers.
Levels of inflammatory markers were markedly higher in patients with sepsis compared with patients after major abdominal surgery and healthy volunteers. After major abdominal surgery, glycocalix markers in human plasma were at levels comparable to patients with sepsis. In patients with sepsis, levels of IL-6 correlated with syndecan-1, ICAM-1, VCAM-1, and lactate, while ICAM-1 furthermore correlated with CRP and lactate levels.
High levels of glycocalix markers indicated that significant flaking of the endothelial glycocalix occurred in patients with sepsis, and to a lesser extent in patients after major abdominal surgery. This novel finding could explain the nonspecific capillary leaking syndrome of patients with sepsis and after major abdominal surgery, and may identify new targets for treating those patient populations.
Journal of Surgical Research 06/2009; 165(1):136-41. · 2.25 Impact Factor
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Resuscitation 04/2009; 80(5):607. · 3.60 Impact Factor
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Thorsten Brenner,
Michael Bernhard,
Matthias Helm,
Sara Doll,
Alfred Völkl,
Nicole Ganion,
Claudia Friedmann,
Marcus Sikinger,
Jürgen Knapp,
Eike Martin,
André Gries
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ABSTRACT: The current guidelines of the European Resuscitation Council (ERC) stipulate that an intraosseous access should be placed if establishing a peripheral venous access for cardiopulmonary resuscitation (CPR) would involve delays. The aim of this study was therefore to compare a manual intraosseous infusion technique (MAN-IO) and a semi-automatic intraosseous infusion system (EZ-IO) using adult human cadavers as a model.
After receiving verbal instruction and giving their written informed consent, the participants of the study were randomized into two groups (group I: MAN-IO, and group II: EZ-IO). In addition to the demographic data, the following were evaluated: (1) Number of attempts required to successfully place the infusion, (2) Insertion time, (3) Occurrence of technical complications and (4) User friendliness.
Evaluation protocols from 84 study participants could be evaluated (MAN-IO: n=39 vs. EZ-IO: n=45). No significant differences were seen in the study participants' characteristics. Insertion times (MW+/-S.D.) of the respective successful attempts were comparable (MAN-IO: 33+/-28s vs. EZ-IO: 32+/-11s). When using the EZ-IO, the access was successfully established significantly more often on the first attempt (MAN-IO: 79.5% vs. EZ-IO: 97.8%; p<0.01). The EZ-IO was also found to have more advantages in terms of technical complications (MAN-IO: 15.4% vs. EZ-IO: 0.0%; p<0.01) and user friendliness (school grading system: MAN-IO: 1.9+/-0.7 vs. EZ-IO: 1.2+/-0.4; p<0.01).
In an adult human cadaver model, the semi-automatic system was proven to be more effective. The EZ-IO gave more successful results, was associated with fewer technical complications, and is user friendlier.
Resuscitation 07/2008; 78(3):314-9. · 3.60 Impact Factor
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Michael Bernhard,
Torben K Becker,
Tim Nowe,
Marko Mohorovicic,
Marcus Sikinger, Thorsten Brenner,
Goetz M Richter,
Boris Radeleff,
Peter-Jürgen Meeder,
Markus W Büchler,
Bernd W Böttiger,
Eike Martin,
André Gries
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ABSTRACT: Successful management of emergency patients with multiple trauma in the hospital resuscitation room depends on the immediate diagnosis and rapid treatment of the most life-threatening injuries. In order to reduce the time spent in the resuscitation room, an in-hospital algorithm was developed in an interdisciplinary team approach with respect to local structures. The aim of the study was to analyse whether this algorithm affects the interval between hospital admission and the completion of diagnostic procedures and the start of life-saving interventions. Moreover, in-hospital mortality was investigated before and after the algorithm was introduced.
In this prospective study, all consecutive trauma patients in the resuscitation room were investigated before (group I, 01/04-10/04) and after (group II, 01/05-11/05) introduction of the algorithm. The times between hospital admission and the end of the diagnostic procedures (ultrasound [sono], chest X-ray [CF], and cranial computed tomography [CCT]), and between hospital admission and the start of life-saving interventions were registered and in-hospital mortality analysed.
In the study period, 170 patients in group I and 199 patients in group II were investigated. Injury severity score (ISS) were comparable between the two groups. The intervals between admission and completion of diagnostic procedures were significantly lower after the algorithm was introduced (mean+/-S.D.): sono (11 +/- 10 min versus 7 +/- 6 min, p < 0.05), CF (21 +/- 12 min versus 12 +/- 9 min, p < 0.01), and CCT (55 +/- 27 min versus 32 +/- 14 min, p < 0.01). Moreover, the interval to the start of life-saving interventions was significantly shorter (126 +/- 90 min versus 51 +/- 20 min, p < 0.01). After introducing the algorithm, in-hospital mortality was reduced significantly from 33.3% to 16.7% (p < 0.05) in the most severely injured patients (ISS>or=25).
The introduction of an algorithm for early management of emergency patients significantly reduced the time spent in the resuscitation room. The periods to completion of sono, CF, and CCT, respectively, and the start of life-saving interventions were significantly shorter after introduction of the algorithm. Moreover, introduction of the algorithm reduced mortality in the most severely injured patients. Although further investigations are needed to evaluate the effects of the Heidelberg treatment algorithm in terms of outcome and mortality, the time reduction in the resuscitation room seems to be beneficial.
Resuscitation 07/2007; 73(3):362-73. · 3.60 Impact Factor
