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Postpartum/peripartum hemorrhage (PPH) is an obstetric emergency complicating 1-10% of all deliveries and is a leading cause of maternal mortality and morbidity worldwide. However, the incidence of PPH differs widely according to the definition and criteria used, the way of measuring postpartum blood loss, and the population being studied with the highest numbers in developing countries. Despite all the significant progress in healthcare, the incidence of PPH is rising due to an incomplete implementation of guidelines, resulting in treatment delays and suboptimal care. A consensus clinical definition of PPH is needed to enable awareness, early recognition, and initiation of appropriate intensive treatment. Unfortunately, the most used definition of PPH based on blood loss ≥500 ml after delivery suffers from inaccuracies in blood loss quantification and is not clinically relevant in most cases, as the amount of blood loss does not fully reflect the severity of bleeding.

The theoretical aspects and benefits of Anesthesia Information Management Systems (AIMS) are well described in literature already. However, certain existing systems are much less researched with most studies concentrating on the USA. In our study, we sent a link to a Google questionnaire to 403 European hospitals and to 382 European authors who have published in the last five years in a renowned anesthesiologic journal. We have not researched AIMS usage in the Czech Republic, as we have covered this topic in our previous study. We asked responders for information on their AIMS (name, vendor, length of use) or to explain why they do not use one. We received 14 responses from the hospitals and 38 responses directly from the authors. With the return rate of 8 per cent we evaluated our study in qualitative terms. Among the 23 respondents that use AIMS there are 12 different systems including two self-developed systems. A number of these systems have not previously been mentioned in the literature. Most use their systems longer than five years but only three respondents are implementing AIMS at the moment. Both these findings show slower progress in this field than in the USA. Typical reasons given from non-users were financial constraints and inability to recognize benefits of AIMS. Incompatibilities with other medical software and medical devices in use were also mentioned. The heterogeneity of AIMS used and perceived barriers corroborate our previous study from the Czech Republic.

The heme-based oxygen sensor protein AfGcHK is a globin-coupled histidine kinase in the soil bacterium Anaeromyxobacter sp. Fw109-5. Its C-terminal functional domain exhibits autophosphorylation activity induced by oxygen binding to the heme-Fe(II) complex located in the oxygen-sensing N-terminal globin domain. A detailed understanding of the signal transduction mechanisms in heme-containing sensor proteins remains elusive. Here, we investigated the role of the globin domain's dimerization interface in signal transduction in AfGcHK. We present a crystal structure of a monomeric imidazole-bound AfGcHK globin domain at 1.8 A resolution, revealing that the helices of the WT globin dimer are under tension and suggesting that Tyr-15 plays a role in both this tension and the globin domain's dimerization. Biophysical experiments revealed that whereas the isolated WT globin domain is dimeric in solution, the Y15A and Y15G variants in which Tyr-15 is replaced with Ala or Gly, respectively, are monomeric. Additionally, we found that although the dimerization of the full-length protein is preserved via the kinase domain dimerization interface in all variants, full-length AfGcHK variants bearing the Y15A or Y15G substitutions lack enzymatic activity. The combined structural and biophysical results presented here indicate that Tyr-15 plays a key role in the dimerization of the globin domain of AfGcHK and that globin domain dimerization is essential for internal signal transduction and autophosphorylation in this protein. These findings provide critical insights into the signal transduction mechanism of the histidine kinase AfGcHK from Anaeromyxobacter.

Epidural analgesia (EPA) is the most effective method of intrapartum pain relief and is considered to be very safe. Recently, it has been used in up to 34% of parturients with EPA and is also associated with maternal temperature elevations during labor. The mechanism of this epidural-associated fever remains incompletely understood. The most likely etiology seems to be non-infectious inflammation caused by an epidural catheter. However, some authors deny this association. They theorize it is caused by selection bias only, as EPA is more often required by women with more painful and prolonged or more complicated labor, where temperature elevation is due to other causes. They point out that in some studies, fever was correlated to EPA only with concurrent placental inflammation. Maternal fever, despite the cause, either infectious or non-infectious origin, carries important clinical and public health implications. Further research that evaluates maternal epidural status and its influence on maternal or neonatal fever could improve sepsis evaluation and lead to worldwide decrease of unnecessary antibio-tic exposure.

IntroductionSupraglottic airway devices represent a less invasive method of airway management than tracheal intubation during general anaesthesia. Their continued development is focused mainly on improvements in the insertion success rate and minimalization of perioperative and postoperative complications. The i-gel Plus is a novel, anatomically preshaped supraglottic airway device which achieves a perilaryngeal seal due to a non-inflatable cuff made of a soft thermoplastic elastomer. The purpose of this trial is to assess the success rate of the i-gel Plus use during elective procedures under general anaesthesia, its intraoperative performance, and the degree of postoperative complications.Methods and analysisThis is a multicenter, prospective, interventional cohort study. The enrolment will take place in seven centers in four European countries. We plan to enrol 2000 adult patients in total, who are scheduled for elective surgery under general anaesthesia, and with an indication for use of a supraglottic airway device for management of their airway. The study is projected to run over a period of 18 months. The primary outcome of the study is the total success rate of the i-gel Plus insertion in terms of successful ventilation and oxygenation through the device. Secondary outcomes include perioperative parameters, such as insertion time, seal/leak pressures, number of insertion attempts, and postoperative adverse events and complications. Postoperative follow-up will be performed at 1 hour, 24 hours in all patients, and for selected patients at 3 and 6 months.Ethics and disseminationThe trial has received the following ethical approvals: General University Hospital Prague, University Hospital Olomouc, University Military Hospital Prague, University Hospital Barcelona, University Hospital Lodz, Antrim Area Hospital, Craigavon Area Hospital, Office for Research Ethics Committees Northern Ireland. The results will be published in peer-reviewed journals and presented at relevant anaesthesia conferences.Trial registration numberISRCTN86233693ARTICLE SUMMARYStrengths and limitations of this study-The study will provide the first data about the use of the novel supraglottic airway device, the i-gel Plus for maintaining ventilation and oxygenation during anaesthesia.-Broad inclusion criteria and the multicenter, multinational design of the study will allow study of a wide spectrum of populations of different age, gender and ethnicity and thus provide more generalisable results.-Patients showing significant postoperative adverse effects will be followed up for up to 6 months which will provide information about the long-term complication rates of the device.-The main limitation of the study is that the device will be trialled only in selected elective procedures and not as a rescue device or in difficult airway management scenarios.

Aims: The purpose of this international survey was to describe the impact of current practices and techniques of caesarean section on the neonatal Apgar score in the Czech Republic (CZE) and Slovakia (SVK). Methods: All Czech and Slovak departments that provide obstetric anaesthesia were invited to participate in a one-month (November 2015) prospective study that monitored in details all peripartum anaesthetic practices, delivered by anaesthesiologists. Participating centers recorded all data on-line in the CLADE-IS database (Masaryk University, CZE). Results and Discussions. We collected data of 10119 women who delivered 10226 newborns. A caesarean section was recorded in 25.1% of deliveries (CZE 23.2%; SVK 30%). General anaesthesia was used for caesarean section in 37.5% of the cases (CZE 40%, SVK 33%). There was no statistically significant difference in the Apgar score lower than 7 in the 1, 5 or 10 min in groups of general and regional anaesthesia for caesarean section, when only elective sections of in-term babies with birth weight over 2500 g were analyzed. We found no statistically significant differences in the Apgar score in newborns of women intubated for caesarean section in rocuronium (n=21; 2.2%) and suxamethonium (n=889; 93%). Conclusion: We found no difference in neonatal outcomes in groups of general and regional anaesthesia for caesarean section when only out-of-risk newborns were analyzed. The risk factors were identified as follows: an acute caesarean section, preterm babies, birth weight less than 2 500 g, born in perinatological center and multiple pregnancy - second baby. Trial Registration: ClinicalTrials.gov (ID: NCT02380586) https://clinicaltrials.gov/ct2/show/NCT02380586

Epiduralni porodni analgezie představuje nejucinnějsi metodu porodni analgezie, avsak v Ceske republice ne přilis rozsiřenou. Cilem clanku je přibližit teorii metody a popsat jeji prakticke provedeni i možne komplikace.

Videolaryngoscopes may reduce cervical spine movement during tracheal intubation in patients with neck trauma. This manikin study aimed to compare the performance of disposable non-channeled and channeled blades of the King Vision™ videolaryngoscope in simulated cervical spine injury. Fifty-eight anesthesiologists in training intubated the TruMan manikin with the neck immobilized using each blade in a randomized order. The primary outcome was the time needed for tracheal intubation, secondary aims included total success rate, the time required for visualization of the larynx, number of attempts, view of the vocal cords, and subjective assessment of both methods. Intubation time with the channeled blade was shorter, with a median time of 13 s (IQR 9−19) vs. 23 s (14.5−37.5), p < 0.001, while times to visualization of the larynx were similar in both groups (p = 0.54). Success rates were similar in both groups, but intubation with the non-channeled blade required more attempts (1.52 vs. 1.05; p < 0.001). The participants scored the intubation features of the channeled blade significantly higher, while visualization features were scored similarly in both groups. Both blades of the King Vision™ videolaryngoscope are reliable intubation devices in a simulated cervical spine injury in a manikin model when inserted by non-experienced operators. The channeled blade allowed faster intubation of the trachea.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background The purpose of this international survey was to describe the current practices and techniques of labor analgesia in the Czech Republic (CZE) and Slovakia (SVK). Methods All Czech and Slovak departments that provide obstetric anesthesia were invited to participate in a one-month (November 2015) prospective study that monitored in detail all peripartum anesthetic procedures delivered by anesthesiologists. Participating centers recorded all data on-line in the CLADE-IS database (Masaryk University, CZE). Results The response rate was 71% (70 of 95 departments in CZE, 35 of 54 centers in SVK). Participating centers represented 87.7% of all births in CZE and 66.4% of all births in SVK during the study period. Analgesia for labor, administered by anesthesiologists, was recorded in 12.5% of deliveries (CZE 12.1%, SVK 13.4%). Epidural analgesia was used in most of the cases (CZE 97.2%, SVK 99.1%) whereas spinal (CZE 1.4%, SVK 0.9%) or combined spinal-epidural (CZE 0.5%, SVK 0.0%) and intravenous remifentanil analgesia (CZE 2.4%, SVK 0.0%) were used infrequently. One fifth of the labors with analgesia administered by anesthesiologists (CZE 20.2%, SVK 20.5%) terminated in cesarean section. Conclusions Although labor analgesia was available in all Czech and Slovak obstetric centers, only a small proportion of parturients received an effective method of labor pain relief (regional or intravenous analgesia).

Human natural killer receptor protein 1 (NKR-P1, CD161, gene klrb1 ) is a C-type lectin-like receptor of natural killer (NK) cells responsible for recognition of its cognate protein ligand lectin-like transcript 1 (LLT1). NKR-P1 is the single human orthologue of the prototypical rodent NKR-P1 receptors. Naturally, human NKR-P1 is expressed on the surface of NK cells, where it serves as inhibitory receptor; and on T and NKT cells functioning as co-stimulatory receptor promoting secretion of IFNγ. Most notably, it is expressed on Th17 and Tc17 lymphocytes where presumably promotes targeting into LLT1 expressing immunologically privileged niches. We tested effect of different protein tags (SUMO, TRX, GST, MsyB) on expression of soluble NKR-P1 in E. coli. Then we optimized the expression construct of soluble NKR-P1 by preparing a library of expression constructs in pOPING vector containing the extracellular lectin-like domain with different length of the putative N -terminal stalk region and tested its expression in Sf9 and HEK293 cells. Finally, a high-level expression of soluble NKR-P1 was achieved by stable expression in suspension-adapted HEK293S GnTI − cells utilizing pOPINGTTneo expression vector. Purified soluble NKR-P1 is homogeneous, deglycosylatable, crystallizable and monomeric in solution, as shown by size-exclusion chromatography, multi-angle light scattering and analytical ultracentrifugation.

The heme-based oxygen sensor histidine kinase AfGcHK is part of a two-component signal transduction system in bacteria. O2 binding to the Fe(II) heme complex of its N-terminal globin domain strongly stimulates autophosphorylation at His183 in its C-terminal kinase domain. The 6-coordinate heme Fe(III)-OH− and -CN− complexes of AfGcHK are also active, but the 5-coordinate heme Fe(II) complex and the heme-free apo-form are inactive. Here, we determined the crystal structures of the isolated dimeric globin domains of the active Fe(III)-CN− and inactive 5-coordinate Fe(II) forms, revealing striking structural differences on the heme-proximal side of the globin domain. Using hydrogen/deuterium exchange coupled with mass spectrometry to characterize the conformations of the active and inactive forms of full-length AfGcHK in solution, we investigated the intramolecular signal transduction mechanisms. Major differences between the active and inactive forms were observed on the heme-proximal side (helix H5), at the dimerization interface (helices H6 and H7 and loop L7) of the globin domain and in the ATP-binding site (helices H9 and H11) of the kinase domain. Moreover, separation of the sensor and kinase domains, which deactivates catalysis, increased the solvent exposure of the globin domain-dimerization interface (helix H6) as well as the flexibility and solvent exposure of helix H11. Together, these results suggest that structural changes at the heme-proximal side, the globin domain-dimerization interface, and the ATP-binding site are important in the signal transduction mechanism of AfGcHK. We conclude that AfGcHK functions as an ensemble of molecules sampling at least two conformational states.

Among other topics related to the visual aspect of cartographic products, current research addresses the problem of user friendliness. The most significant research concerns those products that evolve most rapidly, a typical example being interactive dynamic maps. This group of cartographic works includes products that are relatively challenging for users with respect to their temporally fluid content and the possibility of interactive manipulation. The article begins with a basic discussion of user-friendliness in cartographic products; in this context it addresses the historical development of the notion of cartography as a science, as well as the evolution of the ways in which it has been defined and of its subjects of interest. It demonstrates that, aside from notions of cartography as a technical discipline, it is also of interest from a linguistic point of view for its role as a mean of communication between cartographer and map user. Still greater emphasis is placed on the design aspects of cartographic production. The study offers the example of recent developments in Czech cartographic production, in which the last twenty years have seen a significant differentiation between published cartographic products and amateur cartography generally. This applies to creation as well as user base. Next the article describes a study on the user-friendliness of temporal legends, which are very common in animated maps. The goal of this study, which was conducted during the summer of 2010, was not only to evaluate the given temporal legends, but also to investigate the extent to which users were able to work with temporal variables (with time) in a cartographic product. Among the tools for collecting data was a form of online test. This test posed questions to respondents and automatically measured the amount of time it took them to find their answers. This method was based on the assumption that, given two cartographic works containing similar content, the work which enables the user to find information more quickly is the more user-friendly of the two. The results of the test were then analyzed on the basis of an objective standard for comparing qualities in a cartography work. The authors conclude by suggesting future directions for research on the subject. Výzkum uživatelské vstřícnosti časové legendy v animovaných mapách Vedle technické stránky kartografické tvorby se v současnosti stále více diskutuje o její uživatelské vstřícnosti. Výzkum uživatelské vstřícnosti může být vhodným vodítkem pro odlišení vizualizačních technik, které má smysl dále rozvíjet a technik, které jsou z pohledu uživatele neefektivní. Článek navrhuje a diskutuje tři odlišné typy časové legendy, které řeší rozdílným způsobem samotné znázornění času (dvě odlišné formy časové osy × alfanumerické vyjádření času) a také jeho rychlost a její případné změny. První ze zkoumaných legend vyjadřuje rychlost času rychlostí pohyblivého jezdce, druhá grafickou délkou časových jednotek na časové ose. Poslední, alfanumerická časová legenda, používá ke znázornění rychlosti času speciální, uměle přidaný prvek ve tvaru šipky. Tyto tři navržené časové legendy byly vzájemně porovnány na základě online testu uživatelské vstřícnosti. Do porovnání vstupovaly jak faktory objektivní (jak je uživatel schopen s danou časovou legendou pracovat), tak faktory subjektivní. Z testu vyplynulo, že nejlepší způsob vyjádření času je formou časové osy, kdy je rychlost času vyjádřena proměnnou rychlostí pohyblivého ukazatele („jezdce“). Tento způsob je však v praxi nejběžněji používaný a zůstává proto otázkou, nakolik jsou výsledky testu ovlivněny faktorem zvyku uživatelů. Pro stanovení jasných závěrů by bylo třeba provést větší množství elementárních testů.

The aim of OBAAMA-INT survey (Obstetric Anaesthesia and Analgesia Month Attributes – International) was to audit the current practices in obstetric anaesthesia in the Czech Republic (CZE) and Slovakia (SVK). We also wanted to assess the potential benefit of education of healthcare providers in obstetric anaesthesia during the last 4 years. We already published data about analgesia for labour gathered from OBAAMA-INT survey in International Journal of Obstetric Anesthesia.

Onset times and conditions for intubation after rocuronium versus suxamethonium at cesarean section have been evaluated, but no study thus far has examined the influence of these neuromuscular blocking drugs on the surgical conditions or their effect on the duration of surgery and the ease of fetal delivery. We aimed to compare the surgical conditions for delivery in parturients who received deep neuromuscular block with rocuronium with those who had induction with suxamethonium.Ninety patients undergoing cesarean section under general anesthesia were randomized to receive either rocuronium 0.6 mg/kg or suxamethonium 1 mg/kg for tracheal intubation and delivery. Times to delivery and the quality of surgical conditions, using a five-point Surgical Rating Scale for Delivery (SRSD) ranging from 1 (poor) to 5 (excellent), were evaluated.The median SRSD (range) was found to be significantly better in the rocuronium group [4 (3-5) points vs 3 (2-4) points with suxamethonium (P 0.001)]. Whereas the mean (SD) induction-to-intubation interval was longer with rocuronium [106 (34) s vs 68 (32) s with suxamethonium (95% CI of the difference 24 to 52 s, P 0.001)], the incision-to-delivery interval was shorter in the rocuronium group [147 (68) s vs 196 (51) s with suxamethonium (95% CI of the difference -75 to -24 s, P 0.001)]. The mean induction-to-delivery intervals were similar [268 (73) s vs 276 (63) s, respectively].Whereas the induction-to-delivery intervals were comparable, we found rocuronium superior to suxamethonium in allowing better surgical conditions for fetal delivery, which enabled an easier delivery and a shorter incision-to-delivery interval.

Videolaryngoscopes may improve intubating conditions in obese patients. A total of 110 patients with a body mass index > 35 kg∙m−2 were prospectively randomized to tracheal intubation using non-channeled Glidescope Titanium or channeled King Vision videolaryngoscope. The primary outcome was the time to tracheal intubation. Secondary outcomes included: total success rate, number of attempts, the quality of visualization, peri-procedural and post-proceduralcomplications. Time to the first effective breath was shorter with the King Vision (median; 95% CI)—36; 34–39 s vs. 42; 40–50 in the Glidescope group (p = 0.007). The total success rate was higher in the Glidescope group—100% vs. 89.1% (p = 0.03). There was a higher incidence of moderate and difficult laryngoscopy in the King Vision group. No difference was recorded in first attempt success rates, total number of attempts, use of additional maneuvers, intraoperative trauma, or any significant decrease in SpO2 during intubation. No serious complications were noted and the incidence of postoperative complaints was without difference. Although tracheal intubation with King Vision showed shorter time to the first breath, total success was higher in the Glidescope group, and all but one patients where intubation failed with the KingVision were subsequently intubated with the Glidescope.

Tight glucose control (TGC) reduces morbidity and mortality in patients undergoing elective cardiac surgery, but only limited data about its optimal timing are available to date.The purpose of this article was to compare the effects of perioperative vs postoperative initiation of TGC on postoperative adverse events in cardiac surgery patients.This was a single center, single-blind, parallel-group, randomized controlled trial.The setting was an academic tertiary hospital.Participants were 2383 hemodynamically stable patients undergoing major cardiac surgery with expected postoperative intensive care unit treatment for at least 2 consecutive days.Intensive insulin therapy was initiated perioperatively or postoperatively with a target glucose range of 4.4 to 6.1 mmol/L.Adverse events from any cause during postoperative hospital stay were compared.In the whole cohort, perioperatively initiated TGC markedly reduced the number of postoperative complications (23.2% vs 34.1%, 95% confidence interval [CI], 0.60-0.78) despite only minimal improvement in glucose control (blood glucose, 6.6 ± 0.7 vs 6.7 ± 0.8 mmol/L, P.001; time in target range, 39.3% ± 13.7% vs 37.3% ± 13.8%, P.001). The positive effects of TGC on postoperative complications were driven by nondiabetic subjects (21.3% vs 33.7%, 95% CI, 0.54-0.74; blood glucose 6.5 ± 0.6 vs 6.6 ± 0.8 mmol/L, not significant; time in target range, 40.8% ± 13.6% vs 39.7% ± 13.8%, not significant), whereas no significant effect was seen in diabetic patients (29.4% vs 35.1%, 95% CI, 0.66-1.06) despite significantly better glucose control in the perioperative group (blood glucose, 6.9 ± 1.0 vs 7.1 ± 0.8 mmol/L, P.001; time in target range, 34.3% ± 12.7% vs 30.8% ± 11.5%, P.001).Perioperative initiation of intensive insulin therapy during cardiac surgery reduces postoperative morbidity in nondiabetic patients while having a minimal effect in diabetic subjects.

Lectin-like transcript 1 (LLT1, gene clec2d) was identified to be a ligand for the single human NKR-P1 receptor present on NK and NK-T lymphocytes. Naturally, LLT1 is expressed on the surface of NK cells, stimulating IFN-γ production, and is up-regulated upon activation of other immune cells, e.g. TLR-stimulated dendritic cells and B cells or T cell receptor-activated T cells. While in normal tissues LLT1:NKR-P1 interaction (representing an alternative "missing-self" recognition system) play an immunomodulatory role in regulation of crosstalk between NK and antigen presenting cells, LLT1 is upregulated in glioblastoma cells, one of the most lethal tumors, where it acts as a mediator of immune escape of glioma cells. Here we report transient expression and characterization of soluble His176Cys mutant of LLT1 ectodomain in an eukaryotic expression system of human suspension-adapted HEK293S GnTI(-) cell line with uniform N-glycans. The His176Cys mutation is critical for C-type lectin-like domain stability, leading to the reconstruction of third canonical disulfide bridge in LLT1, as shown by mass spectrometry. Purified soluble LLT1 is homogeneous, deglycosylatable and forms a non-covalent homodimer whose dimerization is not dependent on presence of its N-glycans. As a part of production of soluble LLT1, we have adapted HEK293S GnTI(-) cell line to growth in suspension in media facilitating transient transfection and optimized novel high cell density transfection protocol, greatly enhancing protein yields. This transfection protocol is generally applicable for protein production within this cell line, especially for protein crystallography.

β-N-acetylhexosaminidase from the fungus Aspergillus oryzae is a secreted extracellular enzyme that cleaves chitobiose into constituent monosaccharides. It belongs to the GH 20 glycoside hydrolase family and consists of two N-glycosylated catalytic cores noncovalently associated with two 10-kDa O-glycosylated propeptides. We used X-ray diffraction and mass spectrometry to determine the structure of A. oryzae β-N-acetylhexosaminidase isolated from its natural source. The three-dimensional structure determined and refined to a resolution of 2.3 A revealed that this enzyme is active as a uniquely tight dimeric assembly further stabilized by N- and O-glycosylation. The propeptide from one subunit forms extensive noncovalent interactions with the catalytic core of the second subunit in the dimer, and this chain swap suggests the distinctive structural mechanism of the enzyme's activation. Unique structural features of β-N-acetylhexosaminidase from A. oryzae define a very stable and robust framework suitable for biotechnological applications. The crystal structure reported here provides structural insights into the enzyme architecture as well as the detailed configuration of the active site. These insights can be applied to rational enzyme engineering. DATABASE Structural data are available in the PDB database under the accession number 5OAR. ENZYME β-N-acetylhexosaminidase (EC 3.2.1.52).

The article provides an analysis of the possibilities for the graphic presentation of time in animated cartographic works. After a brief introduction presenting the problem of capturing time and action within the framework of cartographic production, the article mentions methods commonly used for the expression of time in cartographic animations and indicates their weakness: as a rule, these methods don’t reflect the temporo-spatial progression of events that a cartographic work strives to capture. The article then proposes a general approach recommended for the design and creation of temporal legends for animated maps in order to eliminate this flaw. This general approach is then applied to a sample group of cartographic works that depict historical battles.

Background: Glycaemia control (GC) remains an important therapeutic goal in critically ill patients. The enhanced Model Predictive Control (eMPC) algorithm, which models the behaviour of blood glucose (BG) and insulin sensitivity in individual ICU patients with variable blood samples, is an effective, clinically proven computer based protocol successfully tested at multiple institutions on medical and surgical patients with different nutritional protocols. eMPC has been integrated into the B.Braun Space GlucoseControl system (SGC), which allows direct data communication between pumps and microprocessor. The present study was undertaken to assess the clinical performance and safety of the SGC for glycaemia control in critically ill patients under routine conditions in different ICU settings and with various nutritional protocols. Methods: The study endpoints were the percentage of time the BG was within the target range 4.4 - 8.3mmol.l -1, the frequency of hypoglycaemic episodes, adherence to the advice of the SGC and BG measurement intervals. BG was monitored, and insulin was given as a continuous infusion according to the advice of the SGC. Nutritional management (enteral, parenteral or both) was carried out at the discretion of each centre. Results: 17 centres from 9 European countries included a total of 508 patients, the median study time was 2.9 (1.9-6.1) days. The median (IQR) time-in-target was 83.0 (68.7-93.1) % of time with the mean proposed measurement interval 2.0 ± 0.5hours. 99.6 % of the SGC advices on insulin infusion rate were accepted by the user. Only 4 episodes (0.01 % of all BG measurements) of severe hypoglycaemia -1 in 4 patients occurred (0.8 %; 95 % CI 0.02-1.6 %). Conclusion: Under routine conditions and under different nutritional protocols the Space GlucoseControl system with integrated eMPC algorithm has exhibited its suitability for glycaemia control in critically ill patients. Trial registration: ClinicalTrials.gov NCT01523665

OBJECTIVE We performed a randomized trial to compare three insulin-titration protocols for tight glycemic control (TGC) in a surgical intensive care unit: an absolute glucose (Matias) protocol, a relative glucose change (Bath) protocol, and an enhanced model predictive control (eMPC) algorithm. RESEARCH DESIGN AND METHODS A total of 120 consecutive patients after cardiac surgery were randomly assigned to the three protocols with a target glycemia range from 4.4 to 6.1 mmol/l. Intravenous insulin was administered continuously or in combination with insulin boluses (Matias protocol). Blood glucose was measured in 1- to 4-h intervals as requested by the protocols. RESULTS The eMPC algorithm gave the best performance as assessed by time to target (8.8 ± 2.2 vs. 10.9 ± 1.0 vs. 12.3 ± 1.9 h; eMPC vs. Matias vs. Bath, respectively; P < 0.05), average blood glucose after reaching the target (5.2 ± 0.1 vs. 6.2 ± 0.1 vs. 5.8 ± 0.1 mmol/l; P < 0.01), time in target (62.8 ± 4.4 vs. 48.4 ± 3.28 vs. 55.5 ± 3.2%; P < 0.05), time in hyperglycemia >8.3 mmol/l (1.3 ± 1.2 vs. 12.8 ± 2.2 vs. 6.5 ± 2.0%; P < 0.05), and sampling interval (2.3 ± 0.1 vs. 2.1 ± 0.1 vs. 1.8 ± 0.1 h; P < 0.05). However, time in hypoglycemia risk range (2.9–4.3 mmol/l) in the eMPC group was the longest (22.2 ± 1.9 vs. 10.9 ± 1.5 vs. 13.1 ± 1.6; P < 0.05). No severe hypoglycemic episode ( CONCLUSIONS The eMPC algorithm provided the best TGC without increasing the risk of severe hypoglycemia while requiring the fewest glucose measurements. Overall, all protocols were safe and effective in the maintenance of TGC in cardiac surgery patients.

Background Remifentanil has been suggested for its short duration of action to replace standard opioids for induction of general anaesthesia in caesarean section. While the stabilizing effect of remifentanil on maternal circulation has been confirmed, its effect on postnatal adaptation remains unclear, as currently published studies are not powered sufficiently to detect any clinical effect of remifentanil on the newborn. Methods Using a double-blinded randomized design, a total of 151 parturients undergoing caesarean delivery under general anaesthesia were randomized into two groups – 76 patients received a bolus of remifentanil prior to induction, while 75 patients were assigned to the control group. Remifentanil 1 μg/kg was administered 30 seconds before the standard induction of general anaesthesia. The primary outcome measure was an assessment of neonatal adaptation using the Apgar score, while secondary outcomes included the need for respiratory support after delivery and differences in umbilical blood gas analysis (Astrup). Results The incidence of lower Apgar scores between 0 and 7 was significantly higher in the remifentanil group at one minute (25% vs. 9.3% of newborns, p = 0.017); whilst at five minutes and later no Apgar score differences were observed. There was no difference in the need for moderate (nasal CPAP) or intensive (intubation) respiratory support, but significantly more neonates in the remifentanil group required tactile stimulation for breathing support (21% vs. 7% of newborns, p = 0.017). There was no difference in the parameters from umbilical cord blood gas analysis between the groups. Conclusion At a dose of 1 μg/kg, remifentanil prior to induction of general anaesthesia increases the risk of neonatal respiratory depression during first minutes after caesarean delivery but duration of clinical symptoms is short. Trial registration ClinicalTrials.gov: NCT01550640.

BACKGROUND Chronic thromboembolic pulmonary hypertension (CTEPH) in indicated cases can be successfully cured by endartectomy of pulmonary arteries (PEA). Symptomatic nontreated CTEPH has a very poor prognosis; the five-year survival rate in patients with a medium pressure of over 50 mmHg in the main pulmonary artery is as low as 10 %. This kind of operation was previously not available in the Czech Republic. In 2004, a PEA programme was launched at the Cardiocentre of the General Teaching Hospital in Prague in co-operation with the institution of a well known specialist in this field (Prof. Mayer, Johannes Gutenberg University in Mainz, Germany). PATIENTS Between September 2004 and January 2006, 21 patients (14 males and 7 females; average age 48 years) with CTEPH were operated on, after a complex investigation. The mean pressure in the main pulmonary artery in these patients was 54.8 mmHg; 7 patients suffered from coagulopathy. METHOD The new surgical technique, modifications of which are used at most facilities, was developed by Jamieson and Daily at the University of California in San Diego: an arrest of circulation in deep hypothermia to protect the brain is vital for the visualisation of distal branches of the pulmonary artery. RESULTS 21 patients were operated on with a mortality of 4.76 % (1 patient died). Other surgeries performed were suture of a defect of the atrial septum (three times), aortocoronary bypass (three times), and cryoablation of the right atrium for flutter (once). The average circulatory arrest time was 42 minutes, the average total pumping time was 331 minutes, and the average total duration of an operation was 450 minutes; the average duration of mechanical ventilation was 58 hours. Within one month there was a considerable improvement or normalisation of haemodynamic parameters and an increase in the average walking distance on the six-minute walking test by 132 metres. CONCLUSIONS PEA is a curative method for patients with CTEPH with a surgically accessible obstruction of the pulmonary artery. Centralisation of the care of these patients is a rational necessity, as this enables the centre to gain a maximum of experience with this complicated diagnosis and treatment. Multidisciplinary co-operation is a sine qua non for success in these programmes.

OBJECTIVE—To evaluate a fully automated algorithm for the establishment of tight glycemic control in critically ill patients and to compare the results with different routine glucose management protocols of three intensive care units (ICUs) across Europe (Graz, Prague, and London). RESEARCH DESIGN AND METHODS—Sixty patients undergoing cardiac surgery (age 67 ± 9 years, BMI 27.7 ± 4.9 kg/m2, 17 women) with postsurgery blood glucose levels >120 mg/dl (6.7 mmol/l) were investigated in three different ICUs (20 per center). Patients were randomized to either blood glucose management (target range 80–110 mg/dl [4.4–6.1 mmol/l]) by the fully automated model predictive control (MPC) algorithm (n = 30, 10 per center) or implemented routine glucose management protocols (n = 30, 10 per center). In all patients, arterial glucose was measured hourly to describe the glucose profile until the end of the ICU stay but for a maximum period of 48 h. RESULTS—Compared with routine protocols, MPC treatment resulted in a significantly higher percentage of time within the target glycemic range (% median [min–max]: 52 [17–92] vs. 19 [0–71]) over 0–24 h (P < 0.01). Improved glycemic control with MPC treatment was confirmed in patients remaining in the ICU for 48 h (0–24 h: 50 [17–71] vs. 21 [4–67], P < 0.05, and 24–48 h: 65 [38–96] vs. 25 [8–79], P < 0.05, for MPC [n = 16] vs. routine protocol [n = 13], respectively). Two hypoglycemic events ( CONCLUSIONS—The data suggest that the MPC algorithm is safe and effective in controlling glycemia in critically ill postsurgery patients.

Critically ill subjects display high temporal variations in insulin sensitivity, which complicate efficient glucose control by glucose controllers. In the present study, we combined a simple, discrete-time model of glucoregulation with the regularisation method to obtain a time-variant marker of insulin sensitivity from hourly plasma glucose measurements and information about intravenous insulin infusion and parenteral intake in six critically ill subjects studied over 24 to 48h. The focus of the study was to determine “basal insulin requirements„ representing insulin appearance, which maintains normoglycaemia. We observed up to five-fold variations in the basal insulin requirements over a period of 8-10h in a half of the studied subjects. The remaining subjects had virtually unchanged basal insulin requirements. We conclude that considerable heterogeneity exist in the temporal variation of insulin resistance in critically ill subjects.

Four crystal structures of human LLT1, a ligand of human NKR-P1, are reported., Human LLT1 is a C-type lectin-like ligand of NKR-P1 (CD161, gene KLRB1), a C-type lectin-like receptor of natural killer cells. Using X-ray diffraction, the first experimental structures of human LLT1 were determined. Four structures of LLT1 under various conditions were determined: monomeric, dimeric deglycosylated after the first N-acetylglucosamine unit in two forms and hexameric with homogeneous GlcNAc2Man5 glycosylation. The dimeric form follows the classical dimerization mode of human CD69. The monomeric form keeps the same fold with the exception of the position of an outer part of the long loop region. The hexamer of glycosylated LLT1 consists of three classical dimers. The hexameric packing may indicate a possible mode of interaction of C-type lectin-like proteins in the glycosylated form.

BACKGROUND Regular endotracheal tube cuff monitoring may prevent silent aspiration. OBJECTIVES We hypothesised that active management of the cuff of the tracheal tube during deep hypothermic cardiac arrest would reduce silent subglottic aspiration. We also determined to study its effect on postoperative mechanical ventilation and the incidence of postoperative positive tracheal cultures. DESIGN A randomised clinical trial. SETTING The study was conducted in a University Teaching Hospital from September 2008 to November 2009. PATIENTS Twenty-four patients undergoing elective pulmonary endarterectomy were included in the study. INTERVENTION After induction of general anaesthesia and tracheal intubation, the cuff of the tracheal tube was inflated to 25 cmH2O. Following this, 1 ml of methylene blue dye diluted in 2 ml of physiological saline was injected into the hypopharynx. Patients were randomly assigned to active cuff management during cooling and warming (where cuff pressure was monitored and the cuff was reinflated if it dropped below 20 cmH2O, or deflated if pressure exceeded 30 cmH2O) or passive monitoring (where cuff pressure was monitored but volume was not altered). Before weaning from cardiopulmonary bypass, fibreoptic bronchoscopy was performed. Silent aspiration was then diagnosed if blue dye was seen in the trachea below the cuff of the tube. MAIN OUTCOME MEASURES The primary aim of this study was to determine the incidence of silent aspiration. Secondary outcomes included duration of postoperative mechanical ventilation of the lungs and incidence of positive culture of tracheal aspirate. RESULTS Active cuff management patients were younger than controls (51.2 ± 11.6 vs. 63.2 ± 9 years, P = 0.028), but otherwise the two groups were similar. The primary endpoint was reached because we showed that silent aspiration was significantly less frequent in the study group (0/12 vs. 8/12 patients, P = 0.001). Significantly lower intracuff pressures were measured in the control group patients at several timepoints during cooling, just before hypothermic arrest and at all timepoints during rewarming. CONCLUSION We recommend that the cuff of the tracheal tube should be checked regularly during surgery under deep hypothermia, and the cuff pressure adjusted as required.

Aim. In postcardiac surgery patients, we assessed the performance of a system for intensive intravenous insulin therapy using continuous glucose monitoring (CGM) and enhanced model predictive control (eMPC) algorithm.Methods. Glucose control in eMPC-CGM group (n=12) was compared with a control (C) group (n=12) treated by intravenous insulin infusion adjusted according to eMPC protocol with a variable sampling interval alone. In the eMPC-CGM group glucose measured with a REAL-Time CGM system (Guardian RT) served as input for the eMPC adjusting insulin infusion every 15 minutes. The accuracy of CGM was evaluated hourly using reference arterial glucose and Clarke error-grid analysis (C-EGA). Target glucose range was 4.4–6.1 mmol/L.Results. Of the 277 paired CGM-reference glycemic values, 270 (97.5%) were in clinically acceptable zones of C-EGA and only 7 (2.5%) were in unacceptable D zone. Glucose control in eMPC-CGM group was comparable to C group in all measured values (average glycemia, percentage of time above, within, and below target range,). No episode of hypoglycemia (Conclusion. Our data show that the combination of eMPC algorithm with CGM is reliable and accurate enough to test this approach in a larger study population.

Traditionally Gibbs-Donnan coefficients based on the mean charge of plasma proteins are used as the only correction factor in equations describing sodium transport across the dialyzer membrane. This ignores the possible impact of the membrane material. Correction coefficients (CC) of the whole dialyzer were measured during in vivo dialysis as a quotient of dialysate to plasma sodium in an equilibrated state for different membrane materials used in commercially available dialyzers. Their mean value and correlation with total plasma protein content (TPP) were evaluated. CC for the six materials evaluated differed both in the intercept and slope of the re-gression line CC versus TPP: Cuprophan 1: CC = 1.0253 − 0.00017 × TPP; Hemophan 1: CC = 1.119 − 0.00175 × TPP; Hemophan 2: CC = 1.095 − 0.00111 × TPP; PMMA: CC = 1.0353 − 0.00044 × TPP; SCE: CC = 1.114 − 0.00145 × TPP; and Cuprophan 1: CC = 1.0562 − 0.00065 × TPP. The observed differences are attributed to the different charge densities of the membrane materials and suggest that for a precise description of sodium transport, the role of the membrane material needs to be considered.

The urea generation rate (G) and the protein catabolic rate (PCR) have been investigated in two groups of hemodialyzed patients over a whole week cycle, one with zero residual renal function (Kr = 0) dialyzed thrice weekly and the other dialyzed twice weekly with nonzero residual renal function. The two-pool model of urea kinetics was used. No relationship between patients' age and the PCR was found, and also no difference in the PCR between males and females was seen. All patients with a PCR < 0.8 g/kg/day had a midweek predialysis plasma urea level well below 25 mmol/L, which clearly documents the value of a kinetic approach in early detection of patients at risk for malnutrition. In the thrice weekly dialyzed group, a statistically significant relationship was found between PCR and KT/V:PCR = 0.582 + 0.253 x KT/V, r = 0.374 with p < 0.05. In the twice weekly dialyzed group with nonzero Kr, contribution of the residual renal function had to be included into KT/V to reach a level of statistical significance of PCR = 0.697 + 0.18 x KT/V, r = 0.481 with p < 0.05. With regard to values of Kr encountered in the investigated group (0-3.5 ml/min), its influence upon PCR is higher than a volumetrically equal increase in excretorial efficacy of the artificial kidney. The G in the thrice weekly dialyzed group was found to be dependent on the length of the interdialytic interval over which it was evaluated. Over the intervals Friday-Monday, Monday-Wednesday, and Wednesday-Friday the following mean values of G were obtained: 0.155, 0.180, and 0.188 mmol/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

To acquire data for adequate ultrafiltration (UF) control, sodium and potassium balance was investigated during hemodialysis (HD) in 16 hemodialyzed patients. Overall balances were evaluated from concentration measurements of the in- and outflowing dialysate and pre- and postdialysis plasma. The diffusive and convective part of the electrolyte removal and its intra- and extracellular space (ICS, ECS) component were calculated. During a 5-h HD, 40-110 mmol of potassium is removed, predominantly by diffusion (72-88%). Calculation shows that 40-70% of the removed amount is taken from the ICS. Sodium's overall HD showed much higher scatter, ranging from positive values to 500 mmol removal. The diffusive component was positive in most cases. By ultrafiltration sodium is removed in all cases. Calculations also showed in all cases that sodium was delivered to the ICS. This is in contradiction with the general belief that exchangeable sodium is distributed solely in ECS (1,2,6,7). This may be a sign of the effort to keep changes of ICS osmotic load at a minimum. Based on the finding of the exchange of sodium for potassium in the cellular wall, a method has been devised to calculate the UF fraction removed from EC (UFEC) expressed as a coefficient KEC = UFEC/UFToT, with UFToT being the total fluid volume removed during the HD session.

Numerous guidelines and algorithms exist to achieve glycemic control. Their strengths and weaknesses are difficult to assess without head-to-head comparison in time-consuming clinical trials. We hypothesized that computer simulations may be useful.Two open-label randomized clinical trials were replicated using computer simulations. One study compared performance of the enhanced model predictive control (eMPC) algorithm at two intensive care units in the United Kingdom and Belgium. The other study compared three glucose control algorithms-eMPC, Matias (the absolute glucose protocol), and Bath (the relative glucose change protocol)-in a single intensive care unit. Computer simulations utilized a virtual population of 56 critically ill subjects derived from routine data collected at four European surgical and medical intensive care units.In agreement with the first clinical study, computer simulations reproduced the main finding and discriminated between the two intensive care units in terms of the sampling interval (1.3 h vs. 1.8 h, United Kingdom vs. Belgium; P 0.01). Other glucose control metrics were comparable between simulations and clinical results. The principal outcome of the second study was also reproduced. The eMPC demonstrated better performance compared with the Matias and Bath algorithms as assessed by the time when plasma glucose was in the target range between 4.4 and 6.1 mmol/L (65% vs. 43% vs. 42% [P 0.001], eMPC vs. Matias vs. Bath) without increasing the risk of severe hypoglycemia.Computer simulations may provide resource-efficient means for preclinical evaluation of algorithms for glycemic control in the critically ill.

Introduction The target of this study was to compare thromboelastography coagulation parameters in pregnant and non-pregnant women. If appropriate, we would propose recommendations for new reference ranges for pregnant women in their third trimester. Materials and methods Prospective observational study, comparing, by using thromboelastography, the blood samples of 60 healthy women in third trimester of pregnancy (group GRAV) to the samples of the control group of 43 healthy non-pregnant fertile women (group NON-GRAV). Selective percentiles were used to determine new reference limits. Results Mean values and standard deviations (SD) in both groups were as follows (GRAV vs NON-GRAV): time r 4.7 min (SD 1.7) vs. 7.8 (SD 2.8); time k 1.5 min (SD 0.5) vs. 2,7 (SD 0,9); alpha angle 69.6° (SD 5.5) vs. 54.4 (SD 11.5); maximum amplitude 71.3 mm (SD 4.5) vs. 63.1 (SD 5.4); coagulation index 2.7 (SD 1.8) vs. -1.9 (SD 3.0); LY60 1.1% (SD 1.8) vs. 4.8 (SD 3.6). Due to statistically significant differences between both groups, we established, based on our results, these new thromboelastography reference limits for pregnant women: time r 2–8 min (“common” range 4–8 min), time k 1–3 min (“common” range 1–4 min), alpha angle 60-77° (“common” range 47-74°), maximum amplitude 64–76 mm (“common” range 55–73 mm), LY60 0–3% (“common” range 0-15%), coagulation index 0–5 (“common” range (− 3) – (+ 3)). Conclusions It may not be suitable to use the same reference ranges for pregnant women as for the general population. Therefore, we suggest new reference limits for thromboelastography in pregnant women.

Minimally invasive techniques to access subcutaneous adipose tissue for glucose monitoring are successfully applied in type1 diabetic and critically ill patients. During critical illness, the addition of a lactate sensor might enhance prognosis and early intervention. Our objective was to evaluate SAT as a site for lactate measurement in critically ill patients. In 40 patients after major cardiac surgery, arterial blood and SAT microdialysis samples were taken in hourly intervals. Lactate concentrations from SAT were prospectively calibrated to arterial blood. Analysis was based on comparison of absolute lactate concentrations (arterial blood vs. SAT) and on a 6-hour lactate trend analysis, to test whether changes of arterial lactate can be described by SAT lactate. Correlation between lactate readings from arterial blood vs. SAT was highly significant (r2=0.71,P<.001). Nevertheless, 42% of SAT lactate readings and 35% of the SAT lactate trends were not comparable to arterial blood. When a 6-hour stabilization period after catheter insertion was introduced, 5.5% of SAT readings and 41.6% of the SAT lactate trends remained incomparable to arterial blood. In conclusion, replacement of arterial blood lactate measurements by readings from SAT is associated with a substantial shortcoming in clinical predictability in patients after major cardiac surgery.

Context: Hyperglycemia and insulin resistance frequently occur in critically ill patients even without a history of diabetes.Objective: Our objective was to study the role of adipose tissue hormonal production in the development of insulin resistance in cardiac surgery patients.Participants, Interventions, and Settings: Fifteen patients with elective cardiac surgery underwent blood sampling before, at the end, and 6, 12, 24, 48, and 120 h after the end of their operation. Epicardial and sc adipose tissue sampling was done at the beginning and at the end of surgery in the Department of Cardiac Surgery.Main Outcome Measures: We measured serum concentrations and sc and epicardial adipose tissue mRNA expression of IL-6, monocyte chemoattractant protein-1 (MCP-1), TNF-α, leptin, resistin, and adiponectin and sc and epicardial adipose tissue mRNA expression of CD14, CD45, and CD68.Results: The rate of insulin infusion required to maintain euglycemia increased up to 7-fold 12 h after the operation, suggesting the development of insulin resistance. Serum IL-6 levels increased 43-fold 12 h after surgery. MCP-1 peaked 6-fold at the end of surgery. Smaller peaks of TNF-α and leptin appeared 6 and 12 h after surgery, respectively. Resistin levels peaked 4-fold 24 h after surgery, but adiponectin levels were not significantly affected. TNF-α and CD45 mRNA expression increased markedly during the operation in sc adipose tissue. IL-6, resistin, and MCP-1 mRNA expression increased in both sc and epicardial adipose tissue. Leptin, adiponectin, CD14, and CD68 mRNA expression did not change significantly.Conclusions: Both sc and epicardial adipose tissue is a source of proinflammatory cytokines in cardiac surgery patients and may contribute to the development of postoperative insulin resistance.