Kv4 channel expression and kinetics in GABAergic and non-GABAergic rNST neurons.

The rostral nucleus of the solitary tract (rNST) serves as the first central relay in the gustatory system. In addition to synaptic interactions, central processing is also influenced by the ion channel composition of individual neurons. For example, voltage-gated K+ channels such as outward K+ current (IA) can modify the integrative properties of neurons. IA currents are prevalent in rNST projection cells but are also found to a lesser extent in GABAergic interneurons. However, characterization of the kinetic properties of IA, the molecular basis of these currents, as well as the consequences of IA on spiking properties of identified rNST cells is lacking. Here, we show that IA in rNST GABAergic (G+) and non-GABAergic (G-) neurons share a common molecular basis. In both cell types, there was a reduction in IA following treatment with the specific Kv4 channel blocker AmmTx3. However, the kinetics of activation and inactivation of IA in the two cell types were different with G- neurons having significantly more negative half-maximal activation and inactivation values. Likewise, under current clamp, G- cells had significantly longer delays to spike initiation in response to a depolarizing stimulus preceded by a hyperpolarizing prepulse. Computational modeling and dynamic clamp suggest that differences in the activation half-maximum may account for the differences in delay. We further observed evidence for a window current under both voltage clamp and current clamp protocols. We speculate that the location of Kv4.3 channels on dendrites, together with a window current for IA at rest, serves to regulate excitatory afferent inputs.NEW & NOTEWORTHY Here, we demonstrate that the transient outward K+ current IA occurs in both GABAergic and non-GABAergic neurons via Kv4.3 channels in the rostral (gustatory) solitary nucleus. Although found in both cell types, IA is more prevalent in non-GABAergic cells; a larger conductance at more negative potentials leads to a greater impact on spike initiation compared with GABAergic neurons. An IA window current further suggests that IA can regulate excitatory afferent input to the nucleus.

Pulsating Magnetic Reconnection Driven by Three-Dimensional Flux-Rope Interactions.

The dynamics of magnetic reconnection is investigated in a laboratory experiment consisting of two magnetic flux ropes, with currents slightly above the threshold for the kink instability. The evolution features periodic bursts of magnetic reconnection. To diagnose this complex evolution, volumetric three-dimensional data were acquired for both the magnetic and electric fields, allowing key field-line mapping quantities to be directly evaluated for the first time with experimental data. The ropes interact by rotating about each other and periodically bouncing at the kink frequency. During each reconnection event, the formation of a quasiseparatrix layer (QSL) is observed in the magnetic field between the flux ropes. Furthermore, a clear correlation is demonstrated between the quasiseparatrix layer and enhanced values of the quasipotential computed by integrating the parallel electric field along magnetic field lines. These results provide clear evidence that field lines passing through the quasiseparatrix layer are undergoing reconnection and give a direct measure of the nonlinear reconnection rate. The measurements suggest that the parallel electric field within the QSL is supported predominantly by electron pressure; however, resistivity may play a role.

Impact of oxygen sources on performance of the Ventrain(®) ventilation device in an in vitro set-up.

BACKGROUND: The Ventrain(®) (Dolphys Medical, Eindhoven, The Netherlands) is a disposable handheld ventilation device allowing active inspiration and expiration through a transtracheal catheter. This study investigated Ventrain(®) 's performance when used with different clinical oxygen sources in an in vitro set-up. METHODS: Three anesthesia oxygen sources (wall-mounted flowmeter, respirator oxygen outlet port, and anesthesia ventilator circuit) were used at gas flow rates of 6, 9, 12, and 15 l/min. First, the sources' driving pressures (DP), the insufflation pressure (IP), and the flow at the catheter tip were measured using a gas flow analyzer. Tidal volumes (VT) delivered by the Ventrain(®) were assessed by the ASL5000 test lung (respiratory rate: 15 min(-1), I:E = 1:1, compliance: 100 ml/cmH2O, resistance: 3.06 cmH2O/l/s). RESULTS: VT ranged from 82 to 483 ml for inspiration and 82 to 419 ml for expiration. Measured IP, flow, and VT were less dependent on the set gas flow rate but more on the source's DP. With rising DP the IP, the flow at the catheter tip and consequently VT increased. At an approximate target I:E ratio of 1:1, the ratio of inspiratory to expiratory VT increased with higher DP and gas flow rates. CONCLUSION: The oxygen sources resulted in clinically different IP, flows, and VT delivered by the Ventrain(®) at given gas flow rates. This needs to be considered in a clinical emergency situation. Integrating an adjustable pressure valve into Ventrain(®) to allow regulation of the lowest necessary IP would make its use safer.

[Monitoring tidal volumes when using the Ventrain® emergency ventilator]. / Monitoring der Tidalvolumina bei Verwendung des Ventrain® Notfallbeatmungsgerätes.

BACKGROUND: The Ventrain® emergency ventilation device allows active inspiration and expiration through transtracheal catheters or the lumen of an airway exchange catheter. This single-use handheld device is manually operated and driven by an external pressurized oxygen source. The Ventrain® may be used to ventilate patients with a complete or pending upper airway obstruction reducing the risk of barotrauma due to the possibility of active expiration. However tidal volumes (V T) applied and withdrawn with the Ventrain® can only be controlled by visual inspection of chest movements; V T monitoring is not provided. Excessive inspiratory volumes or air trapping due to insufficient expiration may remain clinically undetected until pulmonary trauma and/or cardio-respiratory deterioration occur. Active expiration itself carries the risk of overwhelming lung deflation with the formation of atelectasis. Thus, an inspiratory and expiratory tidal volume monitor is urgently required. The aim of this study was to evaluate efficacy and precision of the Florian respiratory function monitor (RFM) to monitor in- and expiratory V T administered by the Ventrain® emergency ventilation device through a small cannula to the ASL 5000 test lung (ASL). METHODS: In an in-vitro setting the RFM was used with its neonatal flow sensor to monitor inspiratory and expiratory V T applied by the Ventrain® emergency ventilation device through a 2 mm internal diameter (ID) transtracheal catheter to the ASL. Driving flows of 6, 9, 12 and 15 l min(-1) were chosen to vary tidal volumes at a constant respiratory rate of 15 min(-1) and an I:E ratio of 1:1. Experiments were repeated five times with two flow sensors. An initial set-up calibration run was performed to calculate a bias correction factor for inspiratory and expiratory V T measured by the RFM. This bias correction factor was used to simulate a correction of the in the RFM programmed linearization table. In a second, identical setting the experiments were repeated five times with two flow sensors. V T measured by the adjusted RFM were compared with those obtained from the ASL 5000 in this second run and the percentage differences were calculated. Bland Altman analysis was used to investigate the agreement of inspiratory or expiratory VT measured by both methods (ASL and RFM). Calculation of the mean of differences between both methods is given as bias and the 95 % agreement interval as precision. RESULTS: Tidal volumes measured by the ASL ranged from 140 to 675 ml. The percentage correction factor was 16.27 % (2.60 %) during inspiration for V T ranged from 0 to 700 ml and 11.51 % (2.56 %) during expiration for V T of 0 to 225 ml, 7.41 % (2.94 %) for VT 226 to 325 ml and 5.35 % (3.57 %) for TV e > 325 ml. Inspiratory and expiratory tidal volumes measured by the adjusted RFM demonstrated a percentage deviation (mean [SD]) of 2.59 % (1.86 %) during inspiration and 1.66 % (1.14 %) during expiration when compared with the ASL 5000. Bias (precision) of the Bland Altman plot for the adjusted RFM is 2.05 ml (23.20) during inspiration and 4.62 ml (10.40) for expiration. CONCLUSION: The tested respiratory function monitor using hot-wire anemometer technology has the potential to monitor tidal volumes applied by the Ventrain®. With the software thus adapted, the RFM measures precise inspiratory and expiratory tidal volumes within common technical tolerance. This could help perform adequate patient ventilation with Ventrain® and reduce the potential risk of patient trauma.

Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: is there any evidence?

Standard laboratory coagulation tests (SLTs) such as prothrombin time/international normalized ratio or partial thromboplastin time are frequently used to assess coagulopathy and to guide haemostatic interventions. However, this has been challenged by numerous reports, including the current European guidelines for perioperative bleeding management, which question the utility and reliability of SLTs in this setting. Furthermore, the arbitrary definition of coagulopathy (i.e. SLTs are prolonged by more than 1.5-fold) has been questioned. The present study aims to review the evidence for the usefulness of SLTs to assess coagulopathy and to guide bleeding management in the perioperative and massive bleeding setting. Medline was searched for investigations using results of SLTs as a means to determine coagulopathy or to guide bleeding management, and the outcomes (i.e. blood loss, transfusion requirements, mortality) were reported. A total of 11 guidelines for management of massive bleeding or perioperative bleeding and 64 studies investigating the usefulness of SLTs in this setting were identified and were included for final data synthesis. Referenced evidence for the usefulness of SLTs was found in only three prospective trials, investigating a total of 108 patients (whereby microvascular bleeding was a rare finding). Furthermore, no data from randomized controlled trials support the use of SLTs. In contrast, numerous investigations have challenged the reliability of SLTs to assess coagulopathy or guide bleeding management. There is actually no sound evidence from well-designed studies that confirm the usefulness of SLTs for diagnosis of coagulopathy or to guide haemostatic therapy.

Higher fibrinogen concentrations for reduction of transfusion requirements during major paediatric surgery: A prospective randomised controlled trial.

BACKGROUND: Hypofibrinogenaemia is one of the main reasons for development of perioperative coagulopathy during major paediatric surgery. The aim of this study was to assess whether prophylactic maintenance of higher fibrinogen concentrations through administration of fibrinogen concentrate would decrease the volume of transfused red blood cell (RBCs). METHODS: In this prospective, randomised, clinical trial, patients aged 6 months to 17 yr undergoing craniosynostosis and scoliosis surgery received fibrinogen concentrate (30 mg kg(-1)) at two predefined intraoperative fibrinogen concentrations [ROTEM(®) FIBTEM maximum clot firmness (MCF) of <8 mm (conventional) or <13 mm (early substitution)]. Total volume of transfused RBCs was recorded over 24 h after start of surgery. RESULTS: Thirty children who underwent craniosynostosis surgery and 19 children who underwent scoliosis surgery were treated per protocol. During craniosynostosis surgery, children in the early substitution group received significantly less RBCs (median, 28 ml kg(-1); IQR, 21 to 50 ml kg(-1)) compared with the conventional fibrinogen trigger of <8 mm (median, 56 ml kg(-1); IQR, 28 to 62 ml kg(-1)) (P=0.03). Calculated blood loss as per cent of estimated total blood volume decreased from a median of 160% (IQR, 110-190%) to a median of 90% (IQR, 78-110%) (P=0.017). No significant changes were observed in the scoliosis surgery population. No bleeding events requiring surgical intervention, postoperative transfusions of RBCs, or treatment-related adverse events were observed. CONCLUSIONS: Intraoperative administration of fibrinogen concentrate using a FIBTEM MCF trigger level of <13 mm can be successfully used to significantly decrease bleeding, and transfusion requirements in the setting of craniosynostosis surgery, but not scoliosis. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov NCT01487837.

[Comparison of five video laryngoscopes and conventional direct laryngoscopy : Investigations on simple and simulated difficult airways on the intubation trainer]. / Vergleich von fünf Videolaryngoskopen und direkter konventioneller Laryngoskopie : Untersuchung des einfachen und simulierten schwierigen Atemweg am Intubationstrainer.

INTRODUCTION: Securing the airway with a tracheal tube is essential in emergency situations, in the intensive care setting as well as during anesthesia for surgery and other interventions. Current methods of airway assessment are poor screening tests for predicting difficult direct laryngoscopy due to a generally low positive predictive value; therefore, successful endotracheal intubation requires a high level of expertise, regular training and practice and sometimes additional tools. Currently, several video laryngoscopes (VL) with different designs are commercially available and have been investigated in a wide variety of settings. To our knowledge there is no prospective study evaluating and comparing performance among these three groups of VL; therefore, the aim of this study was to compare performance of five VL and conventional direct laryngoscopy in an intubation manikin model, both in a normal and simulated difficult intubation setting. METHODS: In this study 10 residents, 12 senior staff physicians and 5 anesthesia nurses, all experienced in conventional direct laryngoscopy and inexperienced with VL underwent theoretical and hands-on training with all VL lasting 60 min. Afterwards participants performed intubation with all 5 VL and conventional direct laryngoscopy in a randomized sequence using an intubation manikin with normal intubation settings. Thereafter participants performed intubation in a simulated difficult intubation setting using the same intubation manikin with a neck collar to immobilize the cervical spine. In this study, the C-MAC(®) with Macintosh blade size 3, GlideScope(®) size 3, McGrath(®) series 5, King Vision(®) and Airtraq(®) size 2 were used. Time to intubation served as primary outcome and time to glottis visualization, number of intubation attempts, success rate and subjective evaluation of difficulty served as secondary outcomes. RESULTS: In the normal intubation setting, time to intubation ranged from 16.0 s (conventional direct laryngoscopy) to 34.3 s (McGrath). GlideScope and conventional direct laryngoscopy were successful in 100 % followed by C-MAC (96.7 %), Airtraq (88.9 %), King Vision (77.8 %) and McGrath VL (44.4 %). In the simulated difficult intubation setting, time to intubation ranged between 20.3 s (Airtraq) and 26.7 s (McGrath). Success rate with C-MAC was 100 %, followed by GlideScope (96.7 %), Airtraq (85.2 %), conventional direct laryngoscopy (85.2 %), King Vision (81.5 %) and McGrath VL (70.4 %). CONCLUSION: In the manikin with normal intubation setting, conventional direct laryngoscopy using a Macintosh blade was convincing and superior to any VL used in this study. During simulated difficult intubation, a blade with video transmission, such as C-MAC and the GlideScope were superior compared to conventional direct laryngoscopy and any other VL tested.

[Nutrition and IBD-Consensus of the Austrian Working Group of IBD (Inflammatory Bowel Diseases) of the ÖGGH]. / Ernährung und chronisch entzündliche Darmerkrankungen - ein Konsensus der Arbeitsgruppe chronisch entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie (Austrian Guidelines for nutrition in IBD).

This is a consensus of the Austrian working group of IBD (inflammatory bowel diseases) of the ÖGGH on nutrition in IBD. Malnutrition should be assessed in case of IBD (in 20 - 70 % of Crohn's patients) and weight loss(> 5 % within 3 months) or nutritional deficiencies or after extensive bowel resection and afterwards also treated. Malnutrition should be treated with medical therapy of IBD and also adequate - as far as possible - with oral nutritional therapy particularly because of reduced life quality, risk of opportunistic infections, osteopenia/osteoporosis, longer hospitalisations and higher mortality. Iron homeostasis, serum levels of Vitamin B12- and folic acid, 25-hydroxyvitamin D and zinc should be checked. Therapy with enteral liquid diets is only indicated as therapy of first choice in children and adolescents, but only in rare situations in adults with IBD. There is - up to now - no proven oral diet for maintenance of remission in IBD. Probiotics as E. coli Nissle could be used as alternative to mesalazine for maintenance of remission in patients with ulcerative colitis. A specific dietary counselling is mandatory in patients with ileostoma or short bowel syndrome. Malnutrition of short bowel patients is particularly dependent on the function and length of the remaining bowel, therefore the most effective medical therapy should be administered.

[Intubation with a tube exchanger on an intubation trainer. Influence of tube tip position on successful intubation]. / Intubation über den Tubuswechsler an einem Intubationstrainer. Einfluss der Tubusspitzenposition auf den Intubationserfolg.

BACKGROUND: Securing the airway using a tube exchanger catheter is an important and useful technique in anesthesia. Its success is mainly hampered by tube tip impingement of laryngeal structures. Advancing the tracheal tube along its normal curvature via a tube exchanger catheter has a high risk of tube tip impingement mainly of right laryngeal structures. The authors achieved successful clinical experience by rotating the tracheal tube 90° anticlockwise (ventral tube tip position) before railroading the tube via a tube exchanger catheter or a fiber optic bronchoscope through the larynx. AIM: The aim of the study was to investigate the influence of the tracheal tube tip position while intubating an airway trainer over a tube exchange catheter. MATERIAL AND METHODS: Volunteer anesthetists with varying years of professional experience were asked to intubate an intubation mannequin (Laerdal Airway Management Trainer) using the orotracheal route with an established tube exchange catheter (Cook Airway Exchange Catheter, 11F). Two different brands of tracheal tubes (Rüsch and Covidien, ID 7.0 mm) were used in a randomized order, each with the tracheal tube tip at first positioned right (90°), then ventrally (0°), left (270°) and finally dorsally (180°), resulting in eight intubation attempts for each participant. To ensure the correct tube tip position the tube was withdrawn before every intubation attempt until the tube tip position was visualized. The oropharnyx, larynx, trachea and tube were sufficiently lubricated with silicon spray (Rüsch Silikospray). The tube and airway exchange catheter size selection were made according to the clinical trial of Loudermilk et al. Successful endotracheal intubation without resistance was recorded for each tube tip position and tracheal tube brand. RESULTS: In total 20 anesthetists (13 consultants and 7 residents) with a median of 9.5 years (range 3-37 years) of professional experience participated in the study. Overall 160 intubation attempts were performed, 2 participants showed no successful intubation attempts at all and 38 out of 160 intubation attempts (23.8 %) were successful. Intubation success with the tracheal tube tip placed ventrally (0°) was 60 % followed by the left (270°) and right (90°) tracheal tube tip positions with 27.5 % and 7.5 % intubation success, respectively. With the tube tip placed dorsally (180°) none of the 40 intubation attempts were successful. Intubation attempts with the Rüsch tube were more successful (28.8 %) than those with the Covidien tube (18.8 %). Placing the tracheal tube tip ventrally, the Rüsch tube was twice as successful as the Covidien tube with 16 (80 %) versus 8 attempts (40 %, p = 0.011). There was no correlation between professional experience and intubation success (p = 0.362). CONCLUSION: Tube insertion via an airway exchange catheter or a fiberoptic bronchoscope is a basic technique in anesthesia. Knowledge about the difficulties and their prevention are essential for every anesthetist. The gap between the airway exchange catheter, the fiber bronchoscope and the tube diameters is one of the major reasons for tube tip impingement. This investigation showed that intubation success via a tube exchange catheter, as investigated in an intubation mannequin, is considerably influenced by the tracheal tube tip position. A 90° anticlockwise rotation, placing the tracheal tube tip ventrally, considerably increased intubation success. This is of particular importance if an anesthesia department has no appropriately sized tube exchange catheters or fiber bronchoscope for every age group of patients.

[Adalimumab for the treatment of adult Crohn's disease--update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology]. / Adalimumab in der Behandlung des adulten Morbus Crohn--Update eines Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

TNF alpha antibodies have clearly improved the outcome of moderate to severe Crohn's disease. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which can be self-administered subcutaneously. Since August 2012 adalimumab is approved for the treatment of moderately to severely active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Compared to placebo adalimumab can induce significantly more often steroid-free remission and mucosal healing in patients with moderate to severe Crohn's disease, reduce the rate of Crohn's disease-related hospitalisations and surgery and improve health-related quality of life. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to TNF-alpha antibodies and in those previously exposed with a rapid onset of action within days and confirmed maintenance performance over 3 years. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to its low immunogenicity allergic reactions are rare. The update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence on adalimumab for the treatment of Crohn's disease and is aimed to assist as a code of practice in its applications.

[Colorectal cancer: screening and surveillance in inflammatory bowel diseases - consensus of the working group for inflammatory bowel diseases of the Austrian Society of Gastroenterology and Hepatology]. / Kolorektales Karzinom: Screening und Surveillance bei chronisch entzündlichen Darmerkrankungen - Konsensus der Arbeitsgruppe für chronisch entzündliche Darmerkrankungen der ÖGGH.

Patients with ulcerative colitis and Crohn's colitis are at increased risk of colorectal cancer (CRC). This risk is dependent on the duration and extent of disease, inflammatory activity and possible additional risk factors. Thus, the aim is to reduce this risk and to detect dysplastic and malignant lesions at an early stage. The working group for Inflammatory Bowel Diseases (IBD) of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) has developed consensus statements on the following topics: risk of colorectal cancer, screening and surveillance, procedure of surveillance colonoscopy, dysplasia and its management, and chemoprevention. This consensus is intended to increase awareness of the increased risk of CRC in IBD and to support a standardised approach in cancer prevention.

[Insufficiency fractures of the pelvic ring]. / Insuffizienzfrakturen des Beckenrings.

The demographic changes in society automatically lead to an increase in specific diseases and injuries in the older generation. Therefore, the proportion of osteoporotic and fatigue fractures increases in total and also the absolute number of insufficiency fractures of the pelvic ring. In younger people pelvic ring fractures are mostly due high speed trauma. In the elderly this often occurs by low energy trauma or even with no trauma which is then designated as insufficiency fracture. The problematic of such fractures is insufficiently covered in the conventional classification. Conventional radiological diagnostics must often be supplemented by slice imaging procedures. The therapy forms must be more closely adapted to the general condition and physical health of the patient than by classical fractures and the substantially reduced sustainability of osteosynthesis in altered bones must be taken into consideration.

Fully Automatic Method for Reliable Spinal Cord Compartment Segmentation in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Fully automatic quantification methods of spinal cord compartments are needed to study pathologic changes of the spinal cord GM and WM in MS in vivo. We propose a novel method for automatic spinal cord compartment segmentation (SCORE) in patients with MS. MATERIALS AND METHODS: The cervical spinal cords of 24 patients with MS and 24 sex- and age-matched healthy controls were scanned on a 3T MR imaging system, including an averaged magnetization inversion recovery acquisition sequence. Three experienced raters manually segmented the spinal cord GM and WM, anterior and posterior horns, gray commissure, and MS lesions. Subsequently, manual segmentations were used to train neural segmentation networks of spinal cord compartments with multidimensional gated recurrent units in a 3-fold cross-validation fashion. Total intracranial volumes were quantified using FreeSurfer. RESULTS: The intra- and intersession reproducibility of SCORE was high in all spinal cord compartments (eg, mean relative SD of GM and WM: ≤ 3.50% and ≤1.47%, respectively) and was better than manual segmentations (all P < .001). The accuracy of SCORE compared with manual segmentations was excellent, both in healthy controls and in patients with MS (Dice similarity coefficients of GM and WM: ≥ 0.84 and ≥0.92, respectively). Patients with MS had lower total WM areas (P < .05), and total anterior horn areas (P < .01 respectively), as measured with SCORE. CONCLUSIONS: We demonstrate a novel, reliable quantification method for spinal cord tissue segmentation in healthy controls and patients with MS and other neurologic disorders affecting the spinal cord. Patients with MS have reduced areas in specific spinal cord tissue compartments, which may be used as MS biomarkers.

Association between treatment effects on disease progression end points and overall survival in clinical studies of patients with metastatic renal cell carcinoma.

BACKGROUND: The relationship between progression-free survival and time to progression (PFS/TTP) and overall survival (OS) has been demonstrated in a variety of solid tumours but not in metastatic renal cell carcinoma (mRCC). METHODS: A systematic literature search was conducted to identify controlled trials of cytokine or targeted therapies for mRCC reporting information on treatment effects on PFS/TTP and OS for one or more comparison. The associations between treatment effects on PFS/TTP and OS were analysed using linear regression. RESULTS: Thirty-one studies representing 10943 patients, 75 treatment groups, and 41 comparisons were identified. The correlation coefficient between the negative log of the hazard ratio (HR) for PFS/TTP (-ln HR(PFS/TTP)) vs the negative log of the HR for OS (-ln HR(OS)) was 0.80 (P<0.0001). In linear regression, the coefficient on -ln HR(PFS/TTP) vs -ln HR(OS) was 0.64 (95% confidence interval (CI): 0.470.81; R(2)=0.63), suggesting each 10% relative risk reduction (RRR) for PFS/TTP was associated with a 6% RRR for OS. A 1-month gain in median PFS/TTP was associated with a 1.17-month gain in median OS (95% CI: 0.59,1.76; R(2)=0.28). CONCLUSION: In trials of treatments for mRCC, treatment effects on PFS/TTP are strongly associated with treatment effects on OS.

Comparison of thromboelastometry (ROTEM®) with standard plasmatic coagulation testing in paediatric surgery.

BACKGROUND: Thromboelastometry (ROTEM(®)) might be useful to detect intraoperative coagulation disorders early in major paediatric surgery. This observational trial compares this technique to standard coagulation tests. METHODS: Intraoperative blood sampling was obtained in children undergoing elective major surgery. At each time point, standard coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen level] and ROTEM(®) analyses (InTEM, ExTEM, and FibTEM) were performed simultaneously by trained hospital laboratory staff. RESULTS: A total of 288 blood samples from 50 subjects were analysed. While there was a poor correlation between PT and aPTT to ExTEM clotting time (CT) and InTEM CT, respectively, a good correlation was detected between PT and aPTT to clot formation time, and a very good correlation between fibrinogen level and FibTEM assay (r=0.882, P<0.001). Notably, 64% of PT and 94% of aPTT measurements were outside the reference range, while impaired CT was observed in 13% and 6.3%, respectively. Standard coagulation test results were available after a median of 53 min [inter-quartile range (IQR): 45-63 min], whereas 10 min values of ROTEM(®) results were available online after 23 min (IQR: 21-24 min). CONCLUSIONS: PT and aPTT cannot be interchangeably used with ROTEM(®) CT. Based on the results of ROTEM(®), recommended thresholds for PT and aPTT might overestimate the need for coagulation therapy. A good correlation was found between the fibrinogen level and the FibTEM assay. In addition, ROTEM(®) offered faster turnaround times.

Correcting overall survival for the impact of crossover via a rank-preserving structural failure time (RPSFT) model in the RECORD-1 trial of everolimus in metastatic renal-cell carcinoma.

Clinical trials in oncology often allow patients randomized to placebo to cross over to the active treatment arm after disease progression, leading to underestimation of the treatment effect on overall survival as per the intention-to-treat analysis. We illustrate the statistical aspects and practical use of the rank-preserving structural failure time (RPSFT) model with the Fleming-Harrington family of tests to estimate the crossover-corrected treatment effect, and to assess its sensitivity to various weighting schemes in the RECORD-1 trial. The results suggest that the benefit demonstrated in progression-free survival is likely to translate into a robust overall survival benefit.

[Distance from the laryngeal mask grip to endotracheal tube tip. A crucial point during fiberoptic intubation in children]. / Längenverhältnis von Trachealtubus zur Larynxmaske. Kritischer Punkt bei der fiberoptischen Intubation im Kindesalter.

BACKGROUND: Management of difficult airways and difficult intubation differs in pediatric and in adult patients. In conscious children, fiberoptic intubation is not feasible because of limited compliance. The specially designed laryngeal mask for blind tracheal intubation, LMA Fastrach™, is available for adolescents and adults only. Therefore, fiberoptic-guided intubation through a supraglottic airway device (SAD) is a standard technique for the management of difficult intubation in children. While performing the procedure, stabile positioning of the endotracheal tube (ETT) and prevention of dislodgement are critical issues. The relationship between the length of the ETT and the SAD is highly important and was investigated in this in vitro study. MATERIALS AND METHODS: In this study 6 different brands of SAD in the pediatric sizes 1-3 and 2 different ETT brands (cuffed, Microcuff(®), uncuffed, Sheridan PED-SOFT™) were investigated. Using pediatric growth tables, the recommended patient weight for each SAD size was correlated to patient age and then to appropriately sized cuffed and uncuffed ETTs. The ETT size was chosen according to the manufacturer's recommendations (cuffed ETT) and according to the literature (uncuffed ETT). The various SAD-ETT pairs were assessed with regard to differences in their length. After lubrication with silicone the ETT with a firmly attached 15 mm tube adapter was maximally inserted into the SAD and the ETT tip overlapping the SAD cuff was measured. Secondarily, an adapter for fiberoptic procedures was interposed and the measurements repeated. RESULTS: For a defined patient uncuffed ETTs were usually selected with a larger internal diameter (ID) compared to cuffed ETTs. Therefore, the uncuffed ETT is the longer one and will overlap the SAD by a longer tip. Comparing the curved SAD brands AuraOnce™ and Aura-i™, the Aura-i™ devices generally showed shorter tubes resulting in a longer protruding ETT tip (median 1.5 cm, minimum-maximum 1.0-2.4 cm). The straight brands LMA classic™, AuraStraight™ and LMA Unique™ showed similarity in tube length. In comparison with i-gel(®), for the SAD sizes 1-2.5 the former provide a longer projecting ETT tip. Only i-gel(®) together with AuraStraight™ showed the longest overlapping ETT tip for SAD size 3. If a swivel adapter was used during the fiberoptic intubation procedure, the length of the ETT could be critically reduced in relation to the length of the SAD. Using a swivel adapter from VBM Medizintechnik, (Sulz a. N., Germany) a relative reduction in ETT length of 2.3 or 3.2 cm has to be taken into account. CONCLUSIONS: For fiberoptic-guided endotracheal intubation through an SAD, sufficient length of the ETT in relation to the SAD is mandatory. Differences in geometry between SAD and ETT brands have to be considered. The selection of a relatively small SAD in combination with an uncuffed ETT might be advantageous. Redesigned extra long ETTs would be desirable to decrease the risk for ETT dislocation and to increase the safety of the technique. Restrictive use of a swivel adapter during the procedure is important because of further and potentially critical decreases in ETT length. In addition, after successful intubation of the trachea, removal of the SAD via an airway exchange catheter and replacement of the cuffed ETT of choice in the correct position is recommended to secure the airway and provide unimpaired ventilation and oxygenation.

[Low-dose droperidol in children: rescue therapy for persistent postoperative nausea and vomiting]. / "Low-dose"-Droperidol-Gabe bei Kindern: "Rescue"-Therapie gegen persistierende postoperative Übelkeit und Erbrechen.

BACKGROUND: Droperidol had been used as an effective antiemetic since the 1970s but was withdrawn from the market in 2001 because of a black box warning about QT prolongation and possible cardiac arrhythmia after high doses. In the meantime the black box warning has seriously been questioned and parenteral droperidol has again been licensed in 2008. Because droperidol acts on dopaminergic receptors different to 5-HT(3) antagonists and dexamethasone, it could possibly serve as a rescue drug after failed postoperative nausea and vomiting (PONV) prophylaxis. Persistent PONV after the recommended prophylaxis is a significant problem in pediatric anesthesia but a satisfactory strategy has not yet been defined. Therefore a retrospective audit was performed in order to evaluate whether low-dose droperidol (10 µg/kgBW) would be an effective rescue drug for failed antiemetic prophylaxis. PATIENTS AND METHODS: The electronic anesthesia patient data base of the University Children's Hospital Zurich was searched from 2004-2009 for patients who received low-dose droperidol in the postanesthesia care unit as rescue therapy for persistent PONV after antiemetic prophylaxis. Based on the recorded electronic data the effectiveness of low-dose droperidol as PONV rescue therapy and possible side effects were analyzed. RESULTS: A total of 338 patients who received droperidol were found from a total of 34,032 patients and the charts were analyzed. Of these patients 134 were excluded because they had received droperidol for indications other than PONV, 43 patients were excluded because they had not received antiemetic prophylaxis before droperidol and in 17 patients the data were incomplete, leaving 144 patients with an average age of 12.3 years (interquartile range IQR 9.5-15.2 years) for analysis. The upper range of ages resulted from patients with chronic diseases who were still being treated in the Children's Hospital. Low-dose droperidol was given because of persistent nausea to 59 patients (41%) and to 85 patients (59%) for persistent vomiting. Initial antiemetic prophylaxis and/or therapy had consisted of dexamethasone plus tropisetrone in 80 patients and tropisetrone or dexamethasone alone in 64 patients. In 128 patients (89%) rescue therapy with a median dose of 10.9 µg/kgBW droperidol was effective but vomiting persisted in 16 patients (11%). Sedation was the only side effect recorded and this was observed in 39 patients (27%). CONCLUSIONS: Low-dose droperidol (10 µg/kgBW) was found to be effective as rescue medication in pediatric patients experiencing PONV despite various prophylactic antiemetic regimens. No neurological or cardiopulmonary side effects were recorded after this low dosage.

[Comparison of antifog methods in endoscopy. What really helps]. / Vergleich von Antibeschlagmethoden in der Endoskopie. Was wirklich hilft.

BACKGROUND: The use of a flexible or rigid fiberoptic bronchoscope belongs to the standard repertoire in anesthesiology. Besides a lack of training these procedures may be considerably compromised by endoscopic lens fogging. Several antifogging approaches are commercially available but to date no controlled studies regarding the efficacy of these devices in bronchoscopes exists. The aim of the present study was to compare the efficacy of different commercially available anti-fogging techniques for rigid and flexible bronchoscopes. MATERIALS AND METHODS: The study was performed at the department of anesthesia in a university children's hospital. An artificial airway model was created to simulate in vivo conditions with respect to airflow, temperature and atmospheric moisture. A test picture was inserted into the artificial airway for assuring a standardized view through the bronchoscopes. Antifogging efficacy of two liquid antifog solutions (Ultrastop and Anti-Fog), two antifog wipes (Lina Clear and Reso Clear) and an induction endoscope preheater system (used after one and two induction preheating phases) was assessed by video taping of the bronchoscope view of the test picture. In addition the administration of continuous oxygen airflow of 2 l min⁻¹ through the suction channel of the flexible bronchoscope was tested as an alternative method to prevent lens fogging. All final pictures were rated by 10 staff anesthesiologists who were blinded to the antifog devices used. To assess the clinical relevance of the results, ratings were classified into a 5 grade rating scale (ranging from no visualization of any structure to excellent endoscopic view allowing safe endotracheal intubation). In addition, the failure rate of each anti-fog technique was calculated. RESULTS: A total of 300 endoscopic test pictures were taken and assessed. Using the flexible bronchoscope, the use of anti-fog solution (failure rate 3 %) and Lina Clear wipes (failure rate 4%) showed the best results. In the rigid bronchoscope group Ultrastop solution (failure rate 5 %) and Lina Clear wipes (failure rate 3.5 %) showed superior results. The two-time use of the endoscope preheater system was effective using flexible (failure rate 6 %) and rigid bronchoscopes (failure rate 10 %). The application of a continuous oxygen flow of 2 l/min failed to provide a clear endoscopic view (failure rate 93.5 %). CONCLUSIONS: All commercially available antifog liquids and wipes showed slightly different reduction of lens fogging. However, other factors such as frequency of usage, the type of endoscope, hygiene properties as well as cost-effectiveness might have a substantial impact on the comparison of all tested anti-fog devices. The use of an endoscope preheater system might be a conceivable alternative method to reduce lens fogging despite the higher initial cost. However, the multiple use of the preheater system cannot be recommended at present as additional handling procedures to ensure an appropriate but safe temperature of the endoscopic tip should be provided by the manufacturer. Application of a continuous oxygen flow was shown not to be effective in preventing lens fogging using a flexible fiberoptic bronchoscope.