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Most cytoplasmic-replicating negative-strand RNA viruses (NSVs) initiate genome transcription by cap snatching. The source of host mRNAs from which the cytoplasmic NSVs snatch capped-RNA leader sequences has remained elusive. Earlier reports have pointed towards cytoplasmic-RNA processing bodies (P body, PB), although several questions have remained unsolved. Here, the nucleocapsid (N) protein of plant- and animal-infecting members of the order Bunyavirales, in casu Tomato spotted wilt virus (TSWV), Rice stripe virus (RSV), Sin nombre virus (SNV), Crimean-Congo hemorrhagic fever virus (CCHFV) and Schmallenberg virus (SBV) have been expressed and localized in cells of their respective plant and animal hosts. All N proteins localized to PBs as well as stress granules (SGs), but extensively to docking stages of PB and SG. TSWV and RSV N proteins also co-localized with Ran GTPase-activating protein 2 (RanGAP2), a nucleo-cytoplasmic shuttling factor, in the perinuclear region, and partly in the nucleus when co-expressed with its WPP domain containing a nuclear-localization signal. Upon silencing of PB and SG components individually or concomitantly, replication levels of a TSWV minireplicon, as measured by the expression of a GFP reporter gene, ranged from a 30% reduction to a four-fold increase. Upon the silencing of RanGAP homologs in planta, replication of the TSWV minireplicon was reduced by 75%. During in vivo cap-donor competition experiments, TSWV used transcripts destined to PB and SG, but also functional transcripts engaged in translation. Altogether, the results implicate a more complex situation in which, besides PB, additional cytoplasmic sources are used during transcription/cap snatching of cytoplasmic-replicating and segmented NSVs.

OBJECTIVE: After cardiac surgery, major morbidities known to be primary contributors to perioperative mortality are cardiac failure, respiratory failure, renal failure, and the need for mediastinal exploration. The first aim of this study was to ascertain long-term survival in cardiac surgery patients with and without the occurrence of major morbidities to investigate if long-term survival was comparable. The second aim of this study was to evaluate the prevalences and risk factors related to the four major morbidities in this patient population. DESIGN: Retrospective observational outcome study. SETTING: Cardiothoracic intensive care unit at a university hospital. PATIENTS: We included 2,683 of 3,253 consecutive cardiac surgery patients cared for in a uniform fashion. METHODS AND MAIN RESULTS: Perioperative mortality was significantly increased by the occurrence of major morbidity. In-hospital mortality was 0.7% in the absence of major morbidity compared with 72% when all major morbidities occurred. Three-year mortality for the entire study population was 15%, whereas the 3-yr long-term survival was significantly less for patients with morbidities compared with those without. Various independent perioperative risk factors were found for perioperative major morbidity and mortality. CONCLUSIONS: Successful acute treatment and measures to identify and reduce the risk of major morbidities are necessary to improve outcome. In addition, long-term follow-up and management of morbidities are necessary to possibly improve long-term survival. [ABSTRACT FROM AUTHOR]

Esophageal gland secretions from nematodes are believed to include effectors that play important roles in plant parasitism. We have identified a novel gene family encoding secreted proteins specifically expressed in the dorsal esophageal gland of Globodera rostochiensis early in the parasitic cycle, and which contain the B30.2/SPRY domain. The secondary structure of these proteins, named the secreted SPRY domain-containing proteins (SPRYSEC), includes highly conserved regions folding into β-strands interspersed with loops varying in sequence and in length. Mapping sequence diversity onto a three-dimensional structure model of the SPRYSEC indicated that most of the variability is in the extended loops that shape the so-called surface A in the SPRY domains. Seven of nine amino acid sites subjected to diversifying selection in the SPRYSEC are also at this surface. In both yeast-two-hybrid screening using a library from a susceptible tomato and in an in vitro pull-down assay, one of the SPRYSEC interacted with the leucine-rich repeat (LRR) region of a novel coiled-coil nucleotide-binding LRR protein, which is highly similar to members of the SW5 resistance gene cluster. Given that the tomato cultivar used is susceptible to nematode infection, this SPRYSEC could be an evolutionary intermediate that binds to a classical immune receptor but does not yet, or no longer, triggers a resistance response. Alternatively, this SPRYSEC may bind to the immune receptor to downregulate its activity.

Substituted xylan polymers constitute a major part of the hemicellulose fraction of plant cell walls, especially in monocotyledons. Endo-1,4-β-xylanases (EC 3.2.1.8) are capable of hydrolyzing substituted xylan polymers into fragments of random size. Many herbivorous animals have evolved intimate relationships with endosymbionts to exploit their enzyme complexes for the degradation of xylan. Here, we report the first finding of a functional endo-1,4-β-xylanase gene from an animal. The gene (Mi-xyl1) was found in the obligate plant-parasitic root-knot nematode Meloidogyne incognita, and encodes a protein that is classified as a member of glycosyl hydrolase family 5. The expression of Mi-xyl1 is localized in the subventral esophageal gland cells of the nematode. Previous studies have shown that M. incognita has the ability to degrade cellulose and pectic polysaccharides in plant cell walls independent of endosymbionts. Including our current data on Mi-xyl1, we show that the endogenous enzyme complex in root-knot nematode secretions targets essentially all major cell wall carbohydrates to facilitate a stealthy intercellular migration in the host plant.

Various lines of evidence show that local changes in the auxin concentration are involved in the initiation and directional expansion of syncytia induced by cyst nematodes. Analysis of nematode infections on auxin-insensitive tomato and Arabidopsis mutants revealed various phenotypes ranging from complete inhibition of syncytium development to a decrease in hypertrophy and lateral root formation at the infection site. Specific activation of an auxin-responsive promoter confirmed the role of auxin and pointed at a local accumulation of auxin in developing syncytia. Disturbance of auxin gradients by inhibiting polar auxin transport with N-(1-naphthyl)phtalamic acid (NPA) resulted in abnormal feeding cells, which were characterized by extreme galling, massive disordered cell divisions in the cortex, and absence of radial expansion of the syncytium initial toward the vascular bundle. The role of auxin gradients in guiding feeding cell morphogenesis and the cross-talk between auxin and ethylene resulting in a local activation of cell wall degrading enzymes are discussed.

A new strategy has been designed to identify putative pathogenicity factors from the dorsal or subventral esophageal glands of the potato cyst nematode Globodera rostochiensis. Three independent criteria were used for selection. First, genes of interest should predominantly be expressed in infective second-stage juveniles, and not, or to a far lesser extent, in younger developmental stages. For this, gene expression profiles from five different developmental stages were generated with cDNA-AFLP (amplified fragment length polymorphism). Secondly, the mRNA corresponding to such a putative pathogenicity factor should predominantly be present in the esophageal glands of pre-parasitic juveniles. This was checked by in situ hybridization. As a third criterion, these proteinaceous factors should be preceded by a signal peptide for secretion. Expression profiles of more than 4,000 genes were generated and three up-regulated, dorsal gland-specific proteins preceded by signal peptide for secretion were identified. No dorsal gland genes have been cloned before from plant-parasitic nematodes. The partial sequence of these three factors, A4, A18, and A41, showed no significant homology to any known gene. Their presence in the dorsal glands of infective juveniles suggests that these proteins could be involved in feeding cell initiation, and not in migration in the plant root or in protection against plant defense responses. Finally, the applicability of this new strategy in other plant-microbe interactions is discussed.

Background and Goal: Curriculum development for residency training is increasingly challenging in times of financial restrictions and time limitations. Several countries have adopted the CanMEDS framework for medical education as a model into their curricula of specialty training. The purpose of the present study was to validate the competency goals, as derived from CanMEDS, of the Department of Anaesthesiology and Intensive Care Medicine of the Berlin Charité University Medical Centre, by conducting a staff survey. These goals for the qualification of specialists stipulate demonstrable competencies in seven areas: expert medical action, efficient collaboration in a team, communications with patients and family, management and organisation, lifelong learning, professional behaviour, and advocacy of good health. We had previously developed a catalogue of curriculum items based on these seven core competencies. In order to evaluate the validity of this catalogue, we surveyed anaesthetists at our department in regard to their perception of the importance of each of these items. In addition to the descriptive acquisition of data, it was intended to assess the results of the survey to ascertain whether there were differences in the evaluation of these objectives by specialists and registrars., Methods: The questionnaire with the seven adapted CanMEDS Roles included items describing each of their underlying competencies. Each anaesthetist (registrars and specialists) working at our institution in May of 2007 was asked to participate in the survey. Individual perception of relevance was rated for each item on a scale similar to the Likert system, ranging from 1 (highly relevant) to 5 (not at all relevant), from which ratings means were calculated. For determination of reliability, we calculated Cronbach's alpha. To assess differences between subgroups, we performed analysis of variance., Results: All seven roles were rated as relevant. Three of the seven competency goals (expert medical action, efficient collaboration in a team, and communication with patients and family) achieved especially high ratings. Only a few items differed significantly in their average rating between specialists and registrars., Conclusions: We succeeded in validating the relevance of the adapted seven CanMEDS competencies for residency training within our institution. So far, many countries have adopted the Canadian Model, which indicates the great practicability of this competency-based model in curriculum planning. Roles with higher acceptance should be prioritised in existing curricula. It would be desirable to develop and validate a competency-based curriculum for specialty training in anaesthesiology throughout Germany by conducting a national survey to include specialists as well as registrars in curriculum development.

Anticoagulation plays a pivotal role for the efficacy of continuous renal replacement therapy. The equilibrium between avoiding bleeding complications and keeping the system open considering patients} multiple diseases demands an individual and dynamic reasoned anticoagulation regime. For patients at risk of bleeding citrate anticoagulation has shown high efficacy and lesser bleeding complications than the standard heparin or other alternative anticoagulants such as regional protamin-heparin-, prostaglandin-heparin-anticoagulation or no anticoagulation.

The study's objective was to determine the effects of the administration of combinations of C1 esterase inhibitor (C1-INH) with coagulation factor XIII (F XIII) and N-acetylcysteine (NAC) with tirilazad mesylate (TM) on leukocyte adherence and on intestinal functional capillary density during experimental endotoxemia in rats. In a prospective, randomized, controlled animal study, 40 male Wistar rats were divided into 4 groups. Group 1 (CON group) served as control group. Group 2 (LPS group), group 3 (C1-INH+F XIII group) and group 4 (NAC+TM group) received endotoxin infusions (10 mg/kg/h for 2 h). In C1-INH+F XIII group, 100 U/kg b.w. C1-INH and 50 U/kg b.w. F XIII were administered after the first 30 min of endotoxemia. In the NAC+TM group, 150 mg/kg b.w. N-acetylcysteine and 10 mg/kg b.w. Tirilazad mesylate were administered after 30 min of endotoxemia. Leukocyte adherence at venules of the intestinal submucosal layer and functional capillary density in the villi intestinales and in the longitudinal and circular muscle layers were estimated by intravital fluorescence microscopy (IVM). C1-INH+F XIII reduced the count of firmly adherent leukocytes that was increased after LPS administration in the V3 venules (CON group 69 (17-160)/mm2; LPS group 635 (556-814)/mm2; C1-INH+F XIII group 503 (337-646)/mm2). NAC+TM reduced the firmly adherent leukocytes in the V3 venules (NAC+TM group 403 (309-572)/mm2) and in the V1 venules (CON group 55 (16-131)/mm2; LPS group 368 (306-475)/mm2; NAC+TM group 270 (216-308)/mm2) as well. FCD was not impaired after LPS challenge and there was no influence of both combinations on the FCD. We conclude that both drug combinations can reduce the leukocyte adherence in a sepsis model in rats.

Introduction: The study's objective was to determine the effects of the administration of N-acetylcysteine (NAC) and of tirilazad mesylate (TM) on intestinal functional capillary density, mesenteric plasma extravasation, leukocyte adherence and on cytokine release during experimental endotoxemia in rats., Methods: In a prospective, randomized, controlled animal study, 80 male Wistar rats were examined in 2 test series. Both series were divided into 4 groups. Group 1 served as control group (CON group). Group 2 (LPS group), group 3 (NAC group) and group 4 (TM group) received endotoxin infusions (10 mg/kg over 2 h). In NAC group 150 mg/kg body weight NAC was administered after the first 30 minutes of endotoxemia intravenously. In TM group, 10 mg/kg body weight TM was administered after the first 30 minutes of endotoxemia intravenously. Animals of the series 1 underwent studies of leukocyte adherence on submucosal venular endothelium of the small bowel wall and intestinal functional capillary density (FCD) in the intestinal mucosa and the circular as well as the longitudinal muscle layer by intravital fluorescence microscopy (IVM). Plasma levels of interleukin 1beta (IL-1beta), interferone gamma (IFN-gamma) and soluble intercellular adhesion molecule1 (s-ICAM 1) as well as white blood cell count (WBC) were estimated. In the animals of the series 2 mesenteric plasma extravasation was determined by IVM and plasma levels of tumor necrosis factor alpha (TNF-alpha), IL-4, IL-6, IL-10 and malondialdehyde (MDA) were estimated., Results: After LPS administration, FCD in the villi intestinales was unchanged and in the longitudinal muscularis layer it was increased. There was no effect of NAC or TM administration on FCD.Although the plasma extravasation was not significantly influenced by LPS administration, TM administration resulted in a lower plasma extravasation in the TM group compared to the other groups. After endotoxin challenge, the firmly adherence of leukocytes to vascular endothelium as a parameter of leukocyte activation in endotoxemia was increased but NAC or TM administration had no influence on leukocyte adherence. The plasma levels of IL-1beta, IL-6, IL-10, TNF-alpha, IFN-gamma and sICAM-1 were increased in the endotoxemic groups (LPS group, NAC group and TM group) and the WBC was decreased compared to controls. IL-4 levels were unchanged during observation period. Plasma MDA levels were not influenced by LPS administration compared to controls. The administration of NAC resulted in lower sICAM-1 and MDA levels compared to the LPS group. The IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma plasma levels were not influenced by NAC or TM administration., Conclusions: In this posttreatment sepsis model in rats, NAC administration resulted in lower sICAM-1 and MDA levels compared to the LPS treated animals. TM administration reduced the plasma extravasation in this model.

Study Objective: To investigate whether placement, and use of stimulating catheters for interscalene brachial plexus blocks improves short-term postoperative analgesia., Design: Controlled, prospective, randomized, pilot study., Setting: University hospital., Patients: 60 patients undergoing shoulder surgery. INTERVENTIONS AND MAIN MEASUREMENTS: The brachial plexus was identified using a stimulating needle. In conventional catheter group 1 (CC 1), local anesthetic (LA) was injected through the needle and catheters were advanced blindly thereafter. In catheter group 2 (CC 2), catheters were blindly inserted and LA was injected through the catheter. In the stimulating catheter group (SC), LA was injected only after catheter tip location was confirmed by nerve stimulation. Time required to perform the block, pain intensity at rest, and dynamic pain (defined movement: lifting of arm; numeric rating scale, 0-10), patient satisfaction (verbal rating scale, Likert scale), and plasma concentrations of ropivacaine were measured., Main Results: Patients in the SC group had significantly decreased pain scores. The median block performance time was 6 minutes in CC 1 (CI 25%-75%: 4-8 min), 11 minutes in CC 2 (CI 25%-75%: 7-13 min), and 12 minutes in SC (CI 25%-75%: 10-24 min). Patient satisfaction and plasma concentrations of ropivacaine did not differ among the groups., Conclusions: Stimulating catheters for interscalene plexus blocks improve postoperative analgesia at rest in patients undergoing shoulder surgery.

Purpose: The aim of this pilot study was to compare the effect of heparin anticoagulation with and without iloprost administration during continuous renal replacement therapy (CRRT) in critically ill patients., Material and Methods: In a prospective, randomized, controlled pilot study at an intensive care unit at a university hospital, 20 patients requiring CRRT were investigated. Patients were allocated into two groups: group 1, the heparin group; and group 2, the heparin plus 1 ng/kg/min iloprost. In both groups, activated partial thromboplastin time (aPTT) was adjusted to 40-50 sec. Observation time was a maximum of 7 days., Results: Median filter run time was significantly prolonged by iloprost administration to a median of 14 h (13-26 h) compared to 10 h (4-12 h) in the heparin group (p = 0.004). A decrease in platelet count was attenuated by iloprost administration (p = 0.012). There were no bleeding complications in either group. Hemofiltration efficiency did not differ significantly between the groups., Conclusion: Additional administration of iloprost prolonged the filter run time of continuous veno-venous hemofiltration (CVVH) in this setting and attenuated the fall in platelet count during CRRT.

T-cells play a central role in the immune response to injury. Cardiac surgery is associated with significant risk of systemic inflammatory response syndrome and subsequent unbalanced induction of proinflammatory cytokines. As clonidine has immunomodulating properties via reducing sympathetic activity, this study involved the analysis of T-cell function in the early postoperative period in patients undergoing coronary artery bypass graft surgery. Forty patients undergoing cardiac surgery were randomly allocated to one of the following groups: clonidine group (n = 20) [clonidine 1 microg kg(-1) h(-1)] and placebo group (n = 20). Study medication was started after induction of anesthesia and maintained until 6 h after surgery. Blood samples to determine Th1 and Th2 cells and cytotoxic lymphocytes (Tc1 and Tc2 cells) were drawn preoperatively, on admission to the intensive care unit, 6 and 12 h postoperatively as well as on the morning of days 1 and 2 after surgery. In the clonidine group significantly lower levels of Th1/Th2 ratios as well as Tc1/Tc2 ratios were found 6 h postoperatively compared to the placebo group (P < 0.05). Clonidine changed the ratio of T-lymphocyte subpopulations in peripheral blood in favor of a proinflammatory response, which might be favorable for maintaining immune balance after surgery.

Background: Risk factors have been found for prolonged intensive care unit (ICU) stay in cardiac surgery patients in only a few studies; conflicting results have been described. The focus of this study was twofold: first, to evaluate preoperative, intraoperative, and postoperative risk factors for ICU stay greater than 3 days in a cardiac surgery patient population; second, to evaluate long-term survival in cardiac surgery patients with prolonged ICU stay., Methods: Records from 2,683 cardiac surgery patients were retrospectively evaluated. Univariate and multivariate analyses for risk factors were performed for an ICU stay greater than 3 days. Thereafter, 2,563 patients were enrolled in a follow-up study for an observational time of 3 years after surgery., Results: Mortality was dependent on renal, respiratory, and heart failure, as well as age, elevated APACHE II scores, and reexploration. Long-term survival analyses demonstrated a significantly lower survival in patients with longer ICU stay. However, the 6-month to 3-year long-term survival was comparable with survival in patients without prolonged ICU stay., Conclusions: Because of the increasing acuity of patients needing cardiac surgery, it is important to identify those at risk for a prolonged ICU course. It is therefore of paramount interest to implement measures throughout their entire hospital stay that would maximize organ function to improve survival and resource utilization.

Ahead of Print article withdrawn by publisher.

Introduction: The objective of this study was to determine the effects of the administration of the coagulation factor XIII (F XIII) on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia., Methods: In a prospective, randomized, controlled animal study 42 male Wistar rats were divided into three groups. Group 1 served as the control group. Groups 2 (lipopolysaccharide (LPS) group) and 3 (F XIII group) received endotoxin infusions (2.5 mg/kg/h for 2 hours). In group 3, 50 U/kg body weight F XIII was continuously administered during the first 30 minutes of endotoxemia. F XIII levels were measured in all animals. One half of the animals of each group were studied for intestinal functional capillary density (FCD) and leukocyte adherence on venular endothelium by intravital fluorescence microscopy (IVM). In the other half of each group, mesenteric plasma extravasation (FITC-albumin) was determined by IVM., Results: The F XIII level was significantly increased in the F XIII treatment group. In the LPS group, endotoxemia led to a significant reduction of mucosal FCD (-18.5%; p < 0.01 versus control group). F XIII administration in the F XIII group attenuated the decrease in mucosal FCD (-3.7% compared to control; p < 0.05 versus LPS group). During endotoxemia, a significant increase of leukocyte adherence at the endothelium could be noted in the LPS group compared to the control group. Leukocyte adherence at the endothelium and plasma extravasation in the F XIII group did not differ significantly from the LPS group., Conclusion: Factor XIII protected mucosal capillary perfusion against endotoxin-induced impairment in an experimental sepsis model in rats, whereas leukocyte adherence and plasma extravasation remained unchanged.

Introduction: The administration of dopexamine may constitute a therapeutical option to improve hepatosplanchnic perfusion in sepsis. In order to verify this hypothesis, we administered dopexamine in an experimental sepsis model in rats., Methods: This prospective, randomized, controlled laboratory study was conducted in 42 Wistar rats. The animals were divided into 3 groups. Group 1 (CON group) served as control group. The Animals of groups 2 (LPS Group) and 3 received an endotoxin infusion (20 mg/kgfor 15 min). In addition, in group 3 (DPX group) dopexamine was administered 0.5 microg/kg/minover 4 hours. One half of the animals of each group underwent studies of intestinal microvascular blood flow (IMBF) using laser Doppler fluxmetry. In the other half an intravital microscopic evaluation of the leukocyte endothelium cell interaction in the intestinal microcirculation was performed. Functional capillary denstity (FCD) in the intestinal mucosaand the circular as well as the longitudinal muscle layer was estimated., Results: One hour after endotoxin challenge IMBF decreased significantly in the untreated LPS group to 51% compared to baseline (p<0.05). In DPX treated endotoxin animals we found significantly higher values at the level of CON group. The after endotoxin challenge impaired FCD was improved by dopexamine in the longitudinal (DPX + 33% vs. LPS; p <0.05) and in the circular muscle layer (DPX + 48% vs. LPS; p < 0.05) as a result of dopexamine administration. The administration of dopexamine reduced the count of firmly adherent leukocytes when compared to the untreated LPS group (-31%, p<0.05). TNF-alpha plasma levels were reduced by dopexamine infusion (LPS group 3637 +/- 553 pg/mL; DPXgroup 1933 +/- 201 pg/mL) one hour after endotoxin challenge., Conclusions: The administration of dopexamine improved IMBF and FCD as parameters of intestinal microcirculation and reduced leukocyte activation as a parameter of inflammation in experimental sepsis.

Introduction: Endothelial damage accounts greatly for the high mortality in septic shock. Higher expression of mediators (IL-6, IL-8, soluble intercellular adhesion molecule 1 [sICAM-1], soluble endothelial-linked adhesion molecule 1 [sELAM-1]) have been described for non-survivors in comparison with survivors. We investigated the predictive value of the mediators IL-6, IL-8, sELAM-1 and sICAM-1 and their time course in intensive care unit patients who developed septic shock with respect to outcome., Materials and Methods: We measured serum levels of IL-6, IL-8, sELAM-1 and sICAM-1 in 40 intensive care unit patients who developed septic shock. Measurements were performed until death or until resolution of septic shock. Clinical and laboratory data were also recorded., Results: After 48 hours the levels of sELAM-1 and sICAM-1 increased in non-survivors and decreased in survivors. sELAM-1 was predictive for outcome on the third day (P = 0.02) and the fourth day (P = 0.02) after diagnosis of septic shock. This difference in the time course between survivors and non-survivors occurred 7 days before death of the patients (median, 10 days). sICAM-1 levels increased significantly in non-survivors over the study period (P < 0.001). sELAM-1 (P = 0.04), IL-6 (P = 0.04) and IL-8 (P = 0.008) were significantly higher in non-survivors over the whole study period. The age and norepinephrine dose >0.5 mug/kg/min were significantly different between the groups., Conclusion: sELAM-1 showed a markedly opposing course after 48 hours of septic shock. This adhesion molecule may be a useful early predictor of disease severity in the course of septic shock after early initial treatment of the patients, and might suggest considering endothelial-restoring therapy.

Heparin-induced thrombocytopenia type II (HIT II) requires alternative anticoagulation. Hirudin has been effectively used in patients with HIT II scheduled for cardiac surgery. However, bleeding complications were observed in patients with renal impairment. In vitro hemodialysis (HD) has been questioned over its efficacy in eliminating hirudin. Another approach to stop bleeding is the application of recombinant factor VIIa (rFVIIa). We report on a patient with HIT II and chronic renal failure who suffered from severe hirudin-induced bleeding after cardiac surgery who was safely treated with a combined approach of surgical hemostasis, substitution of blood products, HD, and rFVIIa to stop finally bleeding.

Introduction: Hospital-acquired pneumonia after surgery is one of the major causes of septic shock. The excessive inflammatory response appears to be responsible for the increased susceptibility to infections and subsequent sepsis. The primary aim of this study was to investigate immune parameters at the onset of pneumonia, before the development of subsequent septic shock. The secondary aim was to investigate the usefulness of these immune parameters in predicting progression from hospital-acquired pneumonia to septic shock., Methods: This prospective clinical study included 76 patients with the diagnosis of hospital-acquired pneumonia. Approval was obtained from the local institutional ethics committee and relatives of the patients gave informed consent. Of the 76 patients, 29 subsequently developed septic shock. All patients were included within 4 h of establishing the diagnosis of hospital-acquired pneumonia (first collection of blood samples and the analysis of immune mediators). In addition, we defined early (within 12 h of onset of septic shock) and late (within 72 to 96 h of onset) stages of septic shock for the collection of blood samples and the analysis of immune mediators. The immune parameters tumor necrosis factor-alpha, IL-1beta, IL-6, IL-8 and IL-10 as well as the endothelial leucocyte adhesion molecule were analyzed., Results: In the pneumonia group with subsequent septic shock, levels of IL-1beta, IL-6, IL-8 and IL-10 were significantly increased before the onset of septic shock compared to patients without subsequent septic shock. This progression was best predicted by IL-1beta, IL-6, IL-8 and IL-10 (area under the curve > or = 0.8)., Conclusion: At the onset of hospital-acquired pneumonia, a significant relevant systemic cytokine mediated response had already been initiated. It might, therefore, be possible to identify patients at risk for septic shock with these predictive markers during early pneumonia. In addition, immune modulating therapy might be considered as adjuvant therapy.

Introduction: Until now, there has been no gold standard for monitoring delirium in intensive care unit (ICU) patients. In this prospective cohort study, a new score, the Delirium Detection Score (DDS), for severity of delirium in the ICU was evaluated., Methods: After ethical approval and written informed consent, intensive care doctors and nurses assessed 1073 consecutive patients in surgical ICUs using the DDS together with the Ramsay Sedation Scale (RSS). The DDS is composed of eight criteria (orientation, hallucination, agitation, anxiety, seizures, tremor, paroxysmal sweating, and altered sleep- wake rhythm). Additionally, intensive care doctors had to document the Sedation-Agitation Scale (SAS) combined with a defined clinical assessment. For interrater reliability, pair of evaluators assessed patients in a blinded fashion at the same time., Results: RSS1 (9%) was associated with a significantly (p < 0.001) higher DDS than RSS levels 2-6. The DDS increased with the severity of delirium (p < 0.001). The receiver operating characteristics (ROC) for the differentiation between no delirium (SAS < 4) and symptoms of delirium at all (SAS 5-7) showed an area under the curve (AUC) of 0.802 (95% confidential interval (CI): 0.719-0.898; p < 0.001) and 69% sensitivity and 75% specificity was determined. For reliability, a Cronbach's alpha of 0.667 was calculated. The paired comparisons revealed an intraclass correlation between 0.642 and 0.758., Conclusion: The DDS demonstrated good validity with excellent sensitivity and specificity for delirium. The severity of delirium can be more accurately estimated by the DDS. By its composition of several items, the DDS might help to start a symptom-guided therapy immediately.

Introduction: We report a case of twin toddlers who both suffered near drowning but with different post-trauma treatment and course, and different neurological outcomes., Methods and Results: Two twin toddlers (a boy and girl, aged 2 years and 3 months) suffered hypothermic near drowning with protracted cardiac arrest and aspiration. The girl was treated with mild hypothermia for 72 hours and developed acute respiratory dysfunction syndrome and sepsis. She recovered without neurological deficit. The boy's treatment was conducted under normothermia without further complications. He developed an apallic syndrome., Conclusion: Although the twin toddlers experienced the same near drowning accident together, the outcomes with respect to neurological status and postinjury complications were completely different. One of the factors that possibly influenced the different postinjury course might have been prolonged mild hypothermia.

Introduction: Chronic alcoholic patients have a threefold to fourfold increased risk for developing a severe infection or septic shock after surgery, which might be due to altered immune response. The aim of this outcome matched study was to investigate proinflammatory and anti-inflammatory immune parameters during the course of infection and subsequent septic shock in chronic alcoholic patients, and to compare these parameters with those in nonalcoholic patients., Methods: Twenty-eight patients from a cohort of fifty-six with either pneumonia or peritonitis and subsequent septic shock were selected. Fourteen patients were chronic alcoholics whereas fourteen were nonalcoholic patients. Chronic alcoholic patients met criteria (Diagnostic and Statistical Manual of Mental Disorders IV, of the American Psychiatric Association) for alcohol abuse or dependence. Measurements were performed during the onset of infection (within 24 hours after the onset of infection), in early septic shock (within 12 hours after onset of septic shock) and in late septic shock (72 hours after the onset). Blood measurements included proinflammatory and anti-inflammatory cytokines., Results: Chronic alcoholic patients exhibited significantly lower plasma levels of IL-8 (P < 0.010) during the onset of infection than did matched nonalcoholic patients. In early septic shock, chronic alcoholic patients had significantly decreased levels of IL-1beta (P < 0.015), IL-6 (P < 0.016) and IL-8 (P < 0.010). The anti-inflammatory parameters IL-10 and tumour necrosis factor receptors I and II did not differ between alcoholic and nonalcoholic patients., Conclusion: At the onset of infection and during early septic shock, chronic alcoholic patients had lower levels of proinflammatory immune parameters than did nonalcoholic patients. Therefore, immunomodulatory therapy administered early may be considered in chronic alcoholic patients at the onset of an infection because of their altered proinflammatory immune response.

We report a case of right heart failure (RHF) and sepsis with liver insufficiency in a 70-year-old patient after coronary artery bypass graft surgery. Three hours after surgery the patient suddenly developed therapy refractory cardiac arrest caused by RHF. He had to have emergency surgery, under which the graft to the right coronary artery was revised and a right ventricular assist device was implanted. Heart function recovered and the assist device was explanted on day 1 after surgery. Thoracic closure was performed on day 5 after surgery. The patient went into septic shock on day 11. Liver dysfunction developed postoperatively and worsened the course of sepsis. Therefore, MARS (molecular adsorbents recirculating system) dialysis was performed once on day 20 after surgery. Liver function improved after MARS therapy and the patient recovered from sepsis. On day 46 the patient was transferred from the ICU of another hospital to one of the peripheral wards, to be finally discharged on day 67.

Objective: To investigate antibiotic-mediated release of tumour necrosis factor (TNF)-alpha and norharman in patients with hospital-acquired pneumonia with and without additional septic encephalopathy., Design: Prospective observational study with a retrospective post hoc analysis., Setting: Surgical intensive care unit (ICU) at a university hospital., Patients: Thirty-seven patients were consecutively included (9 patients with hospital-acquired pneumonia, 11 patients with hospital-acquired pneumonia and septic encephalopathy, 17 control patients) in the study. Pneumonia was defined according to the criteria of the American Thoracic Society., Interventions: Patients received cephalosporins for antibiotic treatment of hospital-acquired pneumonia. Blood samples were taken before, immediately after and 4 h after application of cephalosporins., Measurements and Results: Of the pneumonia patients, 55% developed septic encephalopathy. ICU stay, complications and mortality were significantly increased. An increased release of TNF-alpha was immediately seen in all pneumonia patients after antibiotics compared to controls, whereas the level did not differ between patients with and without septic encephalopathy. Norharman was significantly increased in pneumonia patients 4 h after antibiotic treatment, in tendency more enhanced in the pneumonia patients without encephalopathy., Conclusions: Patients with hospital-acquired pneumonia and septic encephalopathy had a significantly longer ICU stay with higher mortality rate compared to patients with hospital-acquired pneumonia alone. Antibiotic-mediated TNF-alpha release may induce the kynurenine pathway. TNF-alpha activates indolamine-2,3-dioxygenase with neurotoxic quinolinic acid as the end product. Norharman seems to counteract this mechanism and seems to play a role in neuroprotection. The worse outcome of patients with encephalopathy expresses the need to investigate protective factors and mechanisms.

Background: Besides possible bleeding complications a further problem in anticoagulation during continuous renal replacement therapy (CRRT) is the development of heparin-induced thrombocytopenia type II (HIT II) where further anticoagulation with heparin is contraindicated. The application of continuous hirudin as alternative for heparin caused bleeding complications by comparable filter efficacy. Aim of this prospective-controlled pilot study was to compare the efficacy and safety of intermittent hirudin and continuous heparin for anticoagulation during CRRT in critically ill patients., Methods: 26 patients receiving CRRT were randomly allocated to two groups: Heparin group (14 patients): continuous administration of 250 IU/h heparin, dose was adjusted in 125 IU/h steps with a targeted activated clotting time (ACT) of 180-210 s. Hirudin group (12 patients): initial bolus application of 2-2-5 microg/kg hirudin, dose was adjusted in 2 microg/kg bolus steps with a targeted ecarin clotting time (ECT) >80 s. Observation time was 96 hours., Results: Measured filter run time was virtually longer for heparin. No bleeding complications were observed in the hirudin group, two bleeding complications in the heparin group., Conclusions: Intermittent hirudin can be used safely for anticoagulation in CRRT. However, the in tendency better filter survival for heparin elucidates the need for further investigations to find the right dosage equilibrium between filter clotting and bleeding complications.

Background: N-acetylcysteine (NAC) has been shown to improve splanchnic blood flow in experimental studies. This report evaluates the effects of NAC on liver perfusion and lactate signal intensities in the liver tissue of septic shock patients using proton magnetic resonance imaging and spectroscopy. Furthermore, the monoethylglycinexylidide (MEGX) test was used to investigate hepatic function., Methods: Five septic shock patients received 150 mg/kg body weight NAC as an intravenous bolus injection over 15 min. Lidocaine was injected both prior to and following NAC administration in order to determine MEGX formation. Measurements (hemodynamics, oxygen transport-related variables, blood samples for lactate, liver-related markers) were performed 1 hour before and 1 hour after NAC injection. In addition to the proton magnetic resonance imaging patients received two proton magnetic resonance spectra, one prior to and one 30 min subsequent to the onset of the NAC infusion at a 1.5 Tesla clinical scanner, for measurement of liver perfusion and liver lactate signal intensity., Main Findings: Following NAC infusion, the lactate signal intensity in the liver tissue showed a median decrease of 89% (11-99%), there was a median increase in liver perfusion of 41% (-14 to 559%), and the MEGX serum concentration increased three times (1.52-5.91)., Conclusions: A decrease in the lactate signal intensity in the liver tissue and an increase in the MEGX serum concentration and in liver perfusion might indicate improved liver function as a result of NAC administration. Patients with compromised hepatosplanchnic function, such as patients with septic shock due to peritonitis, may therefore benefit from NAC therapy.