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Background: Cell-free DNA (cfDNA) and extracellular RNA (exRNA) are both suspected to activate coagulation cascades in sepsis. Therefore, our study investigated the influence of plasmatic nucleic acids on coagulation in septic patients in comparison to patients after major abdominal surgery., Materials and Methods: A total of 15 patients with sepsis, 10 postoperative patients, and 10 healthy volunteers were included in this longitudinal study. Blood was collected at sepsis onset and after surgery respectively, as well as after 24, 72 and 168 h. Levels of cfDNA and exRNA were measured by quantitative probe-based polymerase chain reaction. In addition, thromboelastography for coagulation as well as thromboaggregometry for platelet function was conducted., Results: Both cfDNA and exRNA were elevated in patients with sepsis compared with postoperative patients and healthy volunteers. While higher exRNA levels correlated with a faster clotting time and more stable clots, cfDNA correlated with a shorter clotting time but also less fibrinolysis. In addition, higher cfDNA seems to be associated with kidney dysfunction as well as with general markers of cell damage (lactate dehydrogenase and lactate)., Conclusions: Both nucleic acid species might be associated with different effects on coagulation during sepsis, with an overall procoagulatory influence. For this reason, individualized therapeutic approaches in patients suffering from coagulation-associated organ dysfunction might be feasible., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function., Materials and Methods: We performed stimulation of the right cervical branch of the N. vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure-volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay., Results: After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N. vagus was enough during initial LPS infusion., Conclusions: Overall, the N. vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: 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., Materials and Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Lipid peroxidation processes (LPO) are evident in many organ failures. Due to their toxic properties, they are causative for cellular dysfunction at the site of their origin and far beyond. This study was conducted to investigate differences in LPO pattern of patients with established acute respiratory distress syndrome (ARDS) and patients with end-stage liver failure undergoing liver transplantation (LTX) as two mayor prototypes of organ failure., Methods: In this prospective, nonrandomized, controlled trial, we examined LPO by measuring malondialdehyde (MDA), and the volatile aldehydes hexanal and propanal as LPO-markers. Eighteen patients with ARDS, 16 subjects undergoing liver transplantation due to liver failure, and 8 healthy controls were included to the study., Results: ARDS patients showed significantly higher levels in MDA concentrations than LTX and controls, respectively. However, MDA levels of patients with end-stage liver failure were equal to those of controls. Blood concentrations of hexanal and propanal, specific by-products of lipid peroxidation, were elevated in both patient groups, but significantly higher only in LTX. Unexpectedly, hexanal and propanal concentrations were significantly higher in LTX than in ARDS patients. In both patient groups, MDA showed no differences between arterial and mixed venous blood, whereas volatile aldehydes were higher in arterial than in mixed venous compartment., Conclusions: Both ARDS and LTX-patients showed significant evidence of enhanced LPO. However, proportions of MDA and volatile aldehydes differed substantially between the groups. Thus, for the interpretation of LPO markers, disease-specific factors have to be taken into account. Distinctions might be attributable to differences in the effected lipid components or variations in metabolism., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: In this retrospective observational study, we investigated the impact of prior splenectomy on the outcome of patients with complicated peritonitis., Materials and Methods: Of the 284 subjects with severe sepsis or septic shock due to intra-abdominal infection, 27 (9.5%) had undergone splenectomy before the development of that infection and 257 (90.5%) had not undergone splenectomy. The intra-abdominal source of infection was surgically confirmed (index operation)., Results: The group of patients having undergone splenectomy and that of patients not having undergone the procedure were well balanced in age, gender concomitant disease, as well as medication (prior chemotherapy). Twenty-eight-day estimated mortality did not differ between groups (33.3 versus 25.7%; P = 0.39). Ninety-day estimated mortality did not differ either (57.2 versus 49.7%; P = 0.92). Overall survival was equal between the two groups. More patients having undergone splenectomy required dialysis for renal failure (74.0 versus 44.7%; P < 0.01). A Cox regression analysis left age, sepsis-related organ failure assessment (SOFA) score immediately following index-surgery, and need for administration of norepinephrine exceeding 0.1 μg/kg body weight/min as potential predictors of fatal outcome., Conclusions: Our results did not support those of earlier reports suggesting that splenectomy protects against polymicrobial sepsis or septic shock. Regarding most effectiveness criteria (28- and 90-d estimated mortality, duration of mechanical ventilation, length of stay in ICU and in hospital), patients having undergone splenectomy fared as well as did those who had not undergone that procedure; regarding some (need for renal replacement), they fared worse. The effect of splenectomy is not large enough to be proven or ruled out with a limited number of cases., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: 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., Materials and Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2010 Elsevier Inc. All rights reserved.)