The Coagulation Box and a New Hemoglobin-Driven Algorithm for Bleeding Control in Patients with Severe Multiple Traumas

Background: Extensive hemorrhage is the leading cause of death in the first few hours following multiple traumas. Therefore, early and aggressive treatment of clotting disorders could reduce mortality. Unfortunately, the availability of results from commonly performed blood coagulation studies are often delayed whereas hemoglobin (Hb) levels are quickly available. Objectives: In this study, we evaluated the use of initial hemoglobin (Hb) levels as a guide line for the initial treatment of clotting disorders in multiple trauma patients. Patients and Methods: We have developed an Hb-driven algorithm to initiate the initial clotting therapy. The algorithm contains three different steps for aggressive clotting therapy depending on the first Hb value measured in the shock trauma room, (SR) and utilizes fibrinogen, prothrombin complex concentrate (PCC), factor VIIa, tranexamic acid and desmopressin. The above-mentioned drugs were stored in a special “coagulation box” in the hospital pharmacy, and this box could be immediately brought to the SR or operating room (OR) upon request. Despite the use of clotting factors, transfusions using red blood cells (RBC) and fresh frozen plasma (FFP) were performed at an RBC-to-FFP ratio of 2:1 to 1:1. Results: Over a 12-month investigation period, 123 severe multiple trauma patients needing intensive care therapy were admitted to our trauma center (mean age 48 years, mean ISS (injury severity score) 30). Fourteen (11%) patients died; 25 (mean age 51.5 years, mean ISS 53) of the 123 patients were treated using the “coagulation box,” and 17 patients required massive transfusions. Patients treated with the “coagulation box” required an average dose of 16.3 RBC and 12.9 FFP, whereas 17 of the 25 patients required an average dose of 3.6 platelet packs. According to the algorithm, 25 patients received fibrinogen (average dose of 8.25 g), 24 (96%) received PCC (3000 IU.), 14 (56%) received desmopressin (36.6 µg), 13 (52%) received tranexamic acid (2.88 g), and 11 (44%) received factor VIIa (3.7 mg). The clotting parameters markedly improved between SR admission and ICU admission. Of the 25 patients, 16 (64%) survived. The revised injury severity classification (RISC) predicted a survival rate of 41%, which corresponds to a standardized mortality ratio (SMR) of 0.62, which implies a higher survival rate than predicted. Conclusions: An Hb-driven algorithm, in combination with the “coagulation box” and the early use of clotting factors, could be a simple and effective tool for improving coagulopathy in multiple trauma patients

The breast feeding mother and xenon anaesthesia: four case reports. Breast feeding and xenon anaesthesia

<p>Abstract</p> <p>Background</p> <p>Four nursing mothers consented to anaesthesia for urgent surgery only on condition that their ability to breast feed would not be impaired.</p> <p>Methods</p> <p>Following induction of general anaesthesia with propofol and remifentanil, 65-69% xenon supplemented with remifentanil was used as an inhalational anaesthetic for maintenance.</p> <p>Results</p> <p>After finishing surgery the women could be extubated between 2:52 and 7:22 minutes. The women were fully alert just minutes after extubation and spent about 45 minutes in the recovery room before discharge to a regular ward. They resumed regular breast feeding some time later. The propofol concentration in the blood was measured after 0, 30, 90, and 300 minutes and in the milk after 90 and 300 minutes. Just 90 minutes after extubation, the concentration of propofol in the milk was limited (> 3 mg/l) so that pharmacological effects on the babies were excluded after oral intake. Also, no traces of xenon gas were found in the maternal milk at any time. After propofol induction and maintenance of anaesthesia with xenon in combination with a water-soluble short-acting drug like remifentanil, the concentration of propofol in maternal milk is low (> 3 mg/l 90 min after anesthesia) and harmless after oral intake.</p> <p>Conclusions</p> <p>These results, as well as the rapid elimination and absence of metabolism of xenon, are of great interest to nursing mothers. General anaesthesia with propofol for induction only, combined with remifentanil and xenon for maintenance, has not yet been described in breast feeding mothers.</p

The role of effectors in nonhost resistance to filamentous plant pathogens

In nature, most plants are resistant to a wide range of phytopathogens. However, mechanisms contributing to this so-called nonhost resistance (NHR) are poorly understood. Besides constitutive defences, plants have developed two layers of inducible defence systems. Plant innate immunity relies on recognition of conserved pathogen-associated molecular patterns (PAMPs). In compatible interactions, pathogenicity effector molecules secreted by the invader can suppress host defence responses and facilitate the infection process. Additionally, plants have evolved pathogen-specific resistance mechanisms based on recognition of these effectors, which causes secondary defence responses. The current effector-driven hypothesis is that nonhost resistance in plants that are distantly related to the host plant is triggered by PAMP recognition that cannot be efficiently suppressed by the pathogen, whereas in more closely related species, nonhost recognition of effectors would play a crucial role. In this review we give an overview of current knowledge of the role of effector molecules in host and nonhost resistance and place these findings in the context of the model. We focus on examples from filamentous pathogens (fungi and oomycetes), discuss their implications for the field of plant-pathogen interactions and relevance in plant breeding strategies for development of durable resistance in crops

Chemical priming of immunity without costs to plant growth

- β-aminobutyric acid (BABA) induces broad-spectrum disease resistance, but also represses plant growth, which has limited its exploitation in crop protection. BABA perception relies on binding to the aspartyl-tRNA synthetase (AspRS) IBI1, which primes the enzyme for secondary defense activity. This study aimed to identify structural BABA analogues that induce resistance without stunting plant growth. - Using site-directed mutagenesis, we demonstrate that the (L)-aspartic acid-binding domain of IBI1 is critical for BABA perception. Based on interaction models of this domain, we screened a small library of structural BABA analogues for growth repression and induced resistance against biotrophic Hyaloperonospora arabidopsidis (Hpa). - A range of resistance-inducing compounds were identified, of which (R)-β-homoserine (RBH) was the most effective. Surprisingly, RBH acted through different pathways than BABA. RBH-induced resistance (RBH-IR) against Hpa functioned independently salicylic acid, partially relied on camalexin, and was associated with augmented cell wall defense. RBH-IR against necrotrophic Plectosphaerella cucumerina acted via priming of ethylene and jasmonic acid defenses. RBH-IR was also effective in tomato against Botrytis cinerea. Metabolic profiling revealed that RBH, unlike BABA, does not majorly affect plant metabolism. - RBH primes distinct defense pathways against biotrophic and necrotrophic pathogens without stunting plant growth, signifying strong potential for exploitation in crop protection

Recovery index, attentiveness and state of memory after xenon or isoflurane anaesthesia: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Performance of patients immediately after anaesthesia is an area of special interest and so a clinical trial was conducted to compare Xenon with Isoflurane anaesthesia. In order to assess the early cognitive recovery the syndrome short test (SST) according to Erzigkeit (Geromed GmbH) was applied.</p> <p>Methods</p> <p>ASA I and II patients undergoing long and short surgical interventions were randomised to receive either general anaesthesia with Xenon or Isoflurane. The primary endpoint was the validated SST which covering memory disturbances and attentiveness. The test was used on the day prior to intervention, one and three hours post extubation. The secondary endpoint was the recovery index (RI) measured after the end of the inhalation of Xenon or Isoflurane. In addition the Aldrete score was evaluated up to 180 min. On the first post-operative day the patients rated the quality of the anaesthetic using a scoring system from 1-6.</p> <p>Results</p> <p>The demographics of the groups were similar. The sum score of the SST delivered a clear trend one hour post extubation and a statistically significant superiority for Xenon three hours post extubation (p < 0.01). The RI likewise revealed a statistically significant superiority of Xenon 5 minutes post extubation (p < 0.01). The Aldrete score was significantly higher for 45 min. The scoring system results were also better after Xenon anaesthesia (p < 0.001).</p> <p>Conclusions</p> <p>The results show that recovery from anaesthesia and the early return of post-operative cognitive functions are significantly better after Xenon anaesthesia compared to Isoflurane. The results of the RI for Xenon are similar with the previously published results.</p> <p>Trial Registration</p> <p>The trial was registered with the number ISRCTN01110844 <url>http://www.controlled-trials.com/isrctn/pf/01110844</url>.</p

The crystal structure of the Sgt1-Skp1 complex: the link between Hsp90 and both SCF E3 ubiquitin ligases and kinetochores

The essential cochaperone Sgt1 recruits Hsp90 chaperone activity to a range of cellular factors including SCF E3 ubiquitin ligases and the kinetochore in eukaryotes. In these pathways Sgt1 interacts with Skp1, a small protein that heterodimerizes with proteins containing the F-box motif. We have determined the crystal structure of the interacting domains of Saccharomyces cerevisiae Sgt1 and Skp1 at 2.8 Å resolution and validated the interface in the context of the full-length proteins in solution. The BTB/POZ domain of Skp1 associates with Sgt1 via the concave surface of its TPR domain using residues that are conserved in humans. Dimerization of yeast Sgt1 occurs via an insertion that is absent from monomeric human Sgt1. We identify point mutations that disrupt dimerization and Skp1 binding in vitro and find that the interaction with Skp1 is an essential function of Sgt1 in yeast. Our data provide a structural rationale for understanding the phenotypes of temperature-sensitive Sgt1 mutants and for linking Skp1-associated proteins to Hsp90-dependent pathways

EDS1 complexes are not required for PRR responses and execute TNL‐ETI from the nucleus in Nicotiana benthamiana

Heterodimeric complexes incorporating the lipase-like proteins EDS1 with PAD4 or SAG101 are central hubs in plant innate immunity. EDS1 functions encompass signal relay from TIR domain-containing intracellular NLR-type immune receptors (TNLs) towards RPW8-type helper NLRs (RNLs) and, in Arabidopsis thaliana, bolstering of signaling and resistance mediated by cell-surface pattern recognition receptors (PRRs). Increasing evidence points to the activation of EDS1 complexes by small molecule binding. We used CRISPR/Cas-generated mutant lines and agroinfiltration-based complementation assays to interrogate functions of EDS1 complexes in Nicotiana benthamiana. We did not detect impaired PRR signaling in N. benthamiana lines deficient in EDS1 complexes or RNLs. Intriguingly, in assays monitoring functions of SlEDS1-NbEDS1 complexes in N. benthamiana, mutations within the SlEDS1 catalytic triad could abolish or enhance TNL immunity. Furthermore, nuclear EDS1 accumulation was sufficient for N. benthamiana TNL (Roq1) immunity. Reinforcing PRR signaling in Arabidopsis might be a derived function of the TNL/EDS1 immune sector. Although Solanaceae EDS1 functionally depends on catalytic triad residues in some contexts, our data do not support binding of a TNL-derived small molecule in the triad environment. Whether and how nuclear EDS1 activity connects to membrane pore-forming RNLs remains unknown