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Objective: To evaluate the effect of prereperfusion hypothermia initiated in the out-of-hospital setting in awake patients with ST-segment elevation myocardial infarction (STEMI) on myocardial salvage measured by cardiac MRI (CMR)., Methods: Hypothermia was initiated within 6 hours of symptom onset by the emergency medical service with surface cooling pads and cold saline, and continued in the cath lab with endovascular cooling (target temperature: ≤35°C at time of reperfusion). Myocardial salvage index (using CMR) was compared in a randomised, controlled, open-label, endpoint blinded trial to a not-cooled group of patients at day 4±2 after the event., Results: After postrandomisation exclusion of 19 patients a total of 101 patients were included in the intention-to-treat analysis (control group: n=54; hypothermia group: n=47). Target temperature was reached in 38/47 patients (81%) in the intervention group. Study-related interventions resulted in a delay in time from first medical contact to reperfusion of 14 min (control group 89±24 min; hypothermia group 103±21 min; p<0.01). Myocardial salvage index was 0.37 (±0.26) in the control group and 0.43 (±0.27) in the hypothermia group (p=0.27). No differences in cardiac biomarkers or clinical outcomes were found. In a CMR follow-up 6 months after the initial event no significant differences were detected., Conclusion: Out-of-hospital induced therapeutic hypothermia as an adjunct to primary percutaneous coronary intervention did not improve myocardial salvage in patients with STEMI., Trial Registration Number: NCT01777750., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypoxic liver injury (HLI) is a frequent and life-threatening complication in critically ill patients that occurs in up to ten percent of critically ill patients. However, there is a lack of data on HLI following cardiac arrest and its clinical implications on outcome. Aim of this study was to investigate incidence, outcome and functional outcome of patients with HLI after in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA)., Methods: We conducted an analysis of a cardiac arrest registry data over a 7-year period. All patients with non-traumatic OHCA and IHCA with return of spontaneous circulation (ROSC) treated at the emergency department of a tertiary care hospital were included in the study. HLI was defined according to established criteria. Predictors of HLI, occurrence, clinical and neurological outcome were assessed using multivariable regression., Results: Out of 1068 patients after IHCA and OHCA with ROSC, 219 (21%) patients developed HLI. Rate of HLI did not differ significantly in IHCA and OHCA patients. Multivariate regression analysis identified time-to-ROSC [OR 1.18, 95% CI (1.01-1.38); p < 0.05], presence of cardiac failure [OR 2.57, 95% CI (1.65-4.01); p < 0.001] and Charlson comorbidity index [OR 0.83, 95% CI (0.72-0.95); p < 0.01] as independent predictors for occurrence of HLI. Good functional outcome was significantly lower in patients suffering from HLI after 28-days (35% vs. 48%, p < 0.001) and 1-year (34% vs. 44%, p < 0.001). Occurrence of HLI was associated with unfavourable neurological outcome [OR 1.74, 95% CI (1.16-2.61); p < 0.01] in multivariate regression analysis., Conclusion: New onset of HLI is a frequent finding after IHCA and OHCA. HLI is associated with increased mortality, unfavourable neurological and overall outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To assess the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT) serum levels for mid-term mortality in patients presenting with symptomatic atrial fibrillation (AF) to an emergency department., Methods: Non-interventional cohort/follow-up study, including consecutive patients presenting to a tertiary care university emergency department due to symptomatic AF between 2012 and 2016. Multivariable Cox proportional hazard regression models were used to estimate the mortality rates and hazards per 100 patient-years (pry) for NT-proBNP and hs-TnT serum levels in quintiles., Results: 2574 episodes of 1754 patients (age 68 (IQR 58-75) years, female gender 1199 (44%), CHA 2 DS 2 -VASc 3 (IQR 1-4)) were recorded. Following the exclusion of incomplete datasets, 1780 episodes were available for analysis. 162 patients deceased during the mid-term follow-up (median 23 (IQR 4-38) months); the mortality rate was 4.72/100 pry. Hazard for death increased with every quintile of NT-proBNP by 1.53 (HR; 95% CI 1.27 to 1.83; p<0.001) and by 1.31 (HR; 95% CI 1.10 to 1.55; p=0.002) with every quintile of hs-TnT in multivariate Cox-regression analysis. No interaction between NT-proBNP and hs-TnT levels could be observed., Conclusion: Elevated NT-proBNP and hs-TnT levels are independently associated with increased mid-term mortality in patients presenting to an emergency department due to symptomatic AF., Trial Registration Number: NCT03272620; Results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early diagnosis of acute compartment syndrome (ACS) of the leg is essential to improve the outcome. Direct invasive measurement is currently recommended to measure intracompartmental pressure. A non-invasive and reproducible means of making the diagnosis would be a step forward. The purpose of this exploratory study was to investigate the feasibility of non-invasive ultrasound-guided angle measurement as a surrogate of increased pressure in a model of ACS., Methods: A model of ACS was generated by infusion of saline into the anterior compartment of the leg of human cadavers to incrementally increase the intracompartmental pressure from 10 to 100 mmHg. In 40 legs (20 cadavers), the angle (TFA, tibia-fascia angle) between the anterolateral cortex of the tibia and the fascia of the anterior compartment was measured at each 10 mmHg pressure increase using ultrasound in a standardized transversal plane. A multilevel linear regression model was used to estimate intracompartmental pressure from delta TFA (ΔTFA)., Results: TFA (mean [± SD]) increased from 61.0° (± 12.0°) at 10 mmHg up to 81.1° (± 11.1°) at 100 mmHg compartment pressure. Each increase ΔTFA by one degree was associated with an increase in pressure by 3.9 mmHg (95% CI, 3.8-4.0, p  < 0.001)., Conclusions: We found that intracompartmental pressure of the anterior compartment of the calf can be well estimated by ultrasound-based ΔTFA in this post mortem experiment. Our findings indicate that non-invasive TFA measurement is feasible and it is reasonable that this will hold true in real life, but the findings are too preliminary to be used in clinical practice now., Competing Interests: The local institutional review board (Ethics Committee of the Medical University of Vienna) approved this study (121/2010). Consent to participate was not applicable.Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Peritubular capillaritis (ptc), reported by the ptc score, is a major feature of kidney allograft rejection and microvascular inflammation (MVI). MVI sum scores (ptc + glomerulitis score ≥2) are accepted diagnostic surrogates of human leucocyte antigen (HLA)-antibody interaction. However, low-grade inflammation is common and ptc scores (number of leucocytes/capillary) may not mirror all aspects of ptc morphology. Recently we observed a relationship of the diffuse extent of ptc (inflammation of >50% of the renal cortex) with graft loss and significantly higher donor-specific antibody levels, suggesting potential inclusion of diffuse ptc as an additional surrogate of antibody-antigen interaction., Methods: We sought to assess how a combination of ptc score and extent in low-grade inflammation (ptc1) affects transplant glomerulopathy (TG) and graft loss risk. Patients (n = 616) were assessed for MVI in first indication biopsies. Cases with a ptc score of 1 but diffuse extent (ptc1diffuse, g-score = 0, n = 26) were considered additional surrogates of HLA-antibody interaction and compared with MVI ≥2 and MVI <2., Results: The ptc1diffuse and MVI score ≥2 subjects had worse graft survival (42% and 59%) compared with an MVI score <2 (70%) (P = 0.002). The incorporation of ptc1diffuse in the MVI score ≥2 increased the receiver operating characteristics curve for TG [area under the curve (AUC) 0.602; P = 0.008] compared with a Banff MVI score ≥2 (AUC 0.56; P = 0.12); cases with baseline TG were excluded. In multivariate analysis, ptc1diffuse remained independently related to TG (odds ratio 3.89; P = 0.008) and graft loss (hazard ratio 2.64; P = 0.001) even after inclusion of all rejection episodes., Conclusion: An integrated view of ptc morphology including diffuse ptc in MVI is superior for TG and graft loss risk assessment.

Background: Cardiac events after electroconvulsive therapy have been reported sporadically, but a systematic assessment of the risk is missing. The goal of this study was to obtain a robust estimate of the incidence of major adverse cardiac events in adult patients undergoing electroconvulsive therapy., Methods: Systematic review and meta-analysis of studies that investigated electroconvulsive therapy and reported major adverse cardiac events and/or mortality. Endpoints were incidence rates of major adverse cardiac events, including myocardial infarction, arrhythmia, pulmonary edema, pulmonary embolism, acute heart failure, and cardiac arrest. Additional endpoints were all-cause and cardiac mortality. The pooled estimated incidence rates and 95% CIs of individual major adverse cardiac events and mortality per 1,000 patients and per 1,000 electroconvulsive therapy treatments were calculated., Results: After screening of 2,641 publications and full-text assessment of 284 studies, the data of 82 studies were extracted (total n = 106,569 patients; n = 786,995 electroconvulsive therapy treatments). The most commonly reported major adverse cardiac events were acute heart failure, arrhythmia, and acute pulmonary edema with an incidence (95% CI) of 24 (12.48 to 46.13), 25.83 (14.83 to 45.00), and 4.92 (0.85 to 28.60) per 1,000 patients or 2.44 (1.27 to 4.69), 4.66 (2.15 to 10.09), and 1.50 (0.71 to 3.14) per 1,000 electroconvulsive therapy treatments. All-cause mortality was 0.42 (0.11 to 1.52) deaths per 1,000 patients and 0.06 (0.02 to 0.23) deaths per 1,000 electroconvulsive therapy treatments. Cardiac death accounted for 29% (23 of 79) of deaths., Conclusions: Major adverse cardiac events and death after electroconvulsive therapy are infrequent and occur in about 1 of 50 patients and after about 1 of 200 to 500 electroconvulsive therapy treatments.

Aims of this survey were to evaluate prescription patterns for children and adolescents in primary and hospital care settings in Austria and to identify the medicines used most frequently in this population. Prescription data were assessed for the year 2014: for primary care, reimbursement data were obtained from Austrian health insurances; for hospital care, information on medicines dispensed to pediatric wards from hospital pharmacies. Frequencies of medicine use were analyzed by Anatomical Therapeutic Chemical classification system, age groups, and care setting. In primary care, anti-infectives (25%) and medicines for the respiratory system (14%) and for the nervous system (13%); in hospitals, anti-infectives (23%) and medicines for the nervous system (13%) and alimentary tract (12%) were prescribed most frequently. Amoxicillin/beta-lactamase inhibitor, ibuprofen, and paracetamol were the most frequent substances in both primary and hospital care settings. Based on the top 80% prescribed substances, a hit list of 150 pediatric medicines was defined for Austria., Conclusion: This is the first representative and comprehensive survey of medicine use in children and adolescents in Austria, allowing comparison of prescription patterns to other European countries and assessing temporal trends in the future. Moreover, it serves as basis for planned measures to improve rational use of pediatric medicines. What is Known: • Large knowledge gaps exist for medicine use in children and adolescents concerning appropriate dosing, efficacy, and safety aspects. • Off-label medicine use is common in the treatment of children and adolescents. What is New: • We present a comprehensive survey of current prescription patterns for children and adolescents in Austria and define a hit list of pediatric medicines, as basis for developing an evidence-based information platform for health care professionals. • Anti-infectives, medicines for respiratory tract system, and pain medication are most frequently prescribed.

Background: Drug-induced immunosuppression following kidney transplantation is crucial to prevent allograft rejection, but increases risk for infectious disease. Tailoring of drug dosing to prevent both rejection and infection is greatly desirable. The apathogenic and ubiquitous torque teno virus (TTV) reflects immunocompetence of the host and might be a potential candidate for immunologic monitoring., Methods: To assess TTV as an infection biomarker, virus load was prospectively quantified in peripheral blood of 169 consecutive renal allograft recipients at the Medical University Vienna., Results: Patients with infection showed higher TTV levels compared to patients without infection (4.2 × 108 copies/mL [interquartile range, IQR, 2.7 × 107-1.9 × 109] vs 2.9 × 107 [IQR 1.0 × 106-7.2 × 108]; P = .006). Differences in TTV load became evident almost 3 months before infection (median 77 days, IQR 19-98). Each log level of TTV copies/mL increased the odds ratio for infection by 23% (95% confidence interval 1.04-1.45; P = .014). TTV >3.1 × 109 copies/mL corresponded to 90% sensitivity to predict infections. Logistic regression demonstrated independent association between TTV levels and infection., Conclusions: TTV quantification predicts infection after kidney transplantation and might be a potential tool to tailor immunosuppressive drug therapy.

Carbon monoxide (CO) is a leading cause of morbidity and mortality. Treatment focuses on the rapid elimination of CO and management of hypoxia. Oxygen is the cornerstone of therapy, and usually applied via a reservoir face mask. Hyperbaric oxygen therapy eliminates CO faster, but requires extensive equipment and expertise. Non-invasive continuous positive airway pressure (CPAP) ventilation using a tight mask provides a higher inspired fraction of oxygen (FiO 2 ) compared to a reservoir face mask, and increases gas exchange. As this modality is widely available, it might represent a supplemental approach to current treatment of CO poisoning. We present two simultaneous cases of a married couple of 31- and 34-year-old patients, who concurrently suffered CO intoxication due to a faulty gas heater in their apartment. Both reported similar symptoms of headache and weakness, and carboxyhemoglobin (COHb)-levels at admission were 21% in both patients. One patient was treated by non-invasive CPAP-ventilation support with a FiO 2 of 100%, whereas the other was treated by conventional oxygen inhalation. In the patient treated by CPAP, COHb-levels fell quickly to 6% within one hour, and reached 3% after 90 min, whereas it took six hours to reach the same levels in the patient with conventional treatment. This vividly illustrates the potential of CPAP therapy as an alternative to conventional oxygen inhalation in the treatment of CO poisoning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 patients with MPN, including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4 (5.8%) of 69 patients receiving JAK1/2 inhibition compared with 2 (0.36%) of 557 with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 patients with MPN. Considering primary myelofibrosis only (N = 216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) vs 1 (0.54%) of 185 control patients. Lymphomas were of aggressive B-cell type, extranodal, or leukemic with high MYC expression in the absence of JAK2 V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a preexisting B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in Stat1 -/- mice: 16 of 24 mice developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B cells. Transplantations of bone marrow from diseased mice unmasked the outgrowth of a malignant B-cell clone evolving into aggressive B-cell leukemia-lymphoma. We conclude that JAK/STAT1 pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. Detection of a preexisting B-cell clone may identify individuals at risk., (© 2018 by The American Society of Hematology.)

Background: Cardio-pulmonary-resuscitation (CPR) training starting at the age of 12 years is recommended internationally. Training younger children is not recommended because young children lack the physical ability to perform adequate CPR and discouragement to perform CPR later is apprehended. The aim of this study was to answer the following questions: Are younger children discouraged after CPR training? Is discouragement caused by their lack in physical ability to perform adequate chest compressions on a standard manikin and would the use of manikins with a reduced resistance affect their motivation or performance?, Methods: We investigated the motivation and CPR performance of children aged 8-13 years after CPR training on manikins of different chest stiffness in a prospective, randomized, single-blind, controlled trial. 322 children underwent randomization and received 30 minutes CPR training in small groups at school. We used two optically identical resuscitation manikins with different compression resistances of 45kg and 30kg. Motivation was assessed with a self-administered questionnaire. Performance was measured with the Resusci®Anne SkillReporter™., Findings: Motivation after the training was generally high and there was no difference between the two groups in any of the questionnaire items on motivation: Children had fun (98 vs. 99%; P = 0.32), were interested in the training (99 vs. 98%; P = 0.65), and were glad to train resuscitation again in the future (89 vs. 91%; P = 0.89). CPR performance was generally poor (median compression score (8, IQR 1-45 and 29, IQR 11-54; P<0.001) and the mean compression depth was lower in the 45kg-resistance than in the 30kg-resistance group (33±10mm vs. 41±9; P<0.001)., Conclusions: Compression resistances of manikins, though influencing CPR performance, did not discourage 8 to 13 year old children after CPR training. The findings refute the view that young children are discouraged when receiving CPR training even though they are physically not able to perform adequate CPR., Competing Interests: The authors have declared that no competing interest exists.

Background: The unanticipated difficult airway is a potentially life-threatening event during anaesthesia or acute conditions. An unsuccessfully managed upper airway is associated with serious morbidity and mortality. Several bedside screening tests are used in clinical practice to identify those at high risk of difficult airway. Their accuracy and benefit however, remains unclear., Objectives: The objective of this review was to characterize and compare the diagnostic accuracy of the Mallampati classification and other commonly used airway examination tests for assessing the physical status of the airway in adult patients with no apparent anatomical airway abnormalities. We performed this individually for each of the four descriptors of the difficult airway: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation., Search Methods: We searched major electronic databases including CENTRAL, MEDLINE, Embase, ISI Web of Science, CINAHL, as well as regional, subject specific, and dissertation and theses databases from inception to 16 December 2016, without language restrictions. In addition, we searched the Science Citation Index and checked the references of all the relevant studies. We also handsearched selected journals, conference proceedings, and relevant guidelines. We updated this search in March 2018, but we have not yet incorporated these results., Selection Criteria: We considered full-text diagnostic test accuracy studies of any individual index test, or a combination of tests, against a reference standard. Participants were adults without obvious airway abnormalities, who were having laryngoscopy performed with a standard laryngoscope and the trachea intubated with a standard tracheal tube. Index tests included the Mallampati test, modified Mallampati test, Wilson risk score, thyromental distance, sternomental distance, mouth opening test, upper lip bite test, or any combination of these. The target condition was difficult airway, with one of the following reference standards: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation., Data Collection and Analysis: We performed screening and selection of the studies, data extraction and assessment of methodological quality (using QUADAS-2) independently and in duplicate. We designed a Microsoft Access database for data collection and used Review Manager 5 and R for data analysis. For each index test and each reference standard, we assessed sensitivity and specificity. We produced forest plots and summary receiver operating characteristic (ROC) plots to summarize the data. Where possible, we performed meta-analyses to calculate pooled estimates and compare test accuracy indirectly using bivariate models. We investigated heterogeneity and performed sensitivity analyses., Main Results: We included 133 (127 cohort type and 6 case-control) studies involving 844,206 participants. We evaluated a total of seven different prespecified index tests in the 133 studies, as well as 69 non-prespecified, and 32 combinations. For the prespecified index tests, we found six studies for the Mallampati test, 105 for the modified Mallampati test, six for the Wilson risk score, 52 for thyromental distance, 18 for sternomental distance, 34 for the mouth opening test, and 30 for the upper lip bite test. Difficult face mask ventilation was the reference standard in seven studies, difficult laryngoscopy in 92 studies, difficult tracheal intubation in 50 studies, and failed intubation in two studies. Across all studies, we judged the risk of bias to be variable for the different domains; we mostly observed low risk of bias for patient selection, flow and timing, and unclear risk of bias for reference standard and index test. Applicability concerns were generally low for all domains. For difficult laryngoscopy, the summary sensitivity ranged from 0.22 (95% confidence interval (CI) 0.13 to 0.33; mouth opening test) to 0.67 (95% CI 0.45 to 0.83; upper lip bite test) and the summary specificity ranged from 0.80 (95% CI 0.74 to 0.85; modified Mallampati test) to 0.95 (95% CI 0.88 to 0.98; Wilson risk score). The upper lip bite test for diagnosing difficult laryngoscopy provided the highest sensitivity compared to the other tests (P < 0.001). For difficult tracheal intubation, summary sensitivity ranged from 0.24 (95% CI 0.12 to 0.43; thyromental distance) to 0.51 (95% CI 0.40 to 0.61; modified Mallampati test) and the summary specificity ranged from 0.87 (95% CI 0.82 to 0.91; modified Mallampati test) to 0.93 (0.87 to 0.96; mouth opening test). The modified Mallampati test had the highest sensitivity for diagnosing difficult tracheal intubation compared to the other tests (P < 0.001). For difficult face mask ventilation, we could only estimate summary sensitivity (0.17, 95% CI 0.06 to 0.39) and specificity (0.90, 95% CI 0.81 to 0.95) for the modified Mallampati test., Authors' Conclusions: Bedside airway examination tests, for assessing the physical status of the airway in adults with no apparent anatomical airway abnormalities, are designed as screening tests. Screening tests are expected to have high sensitivities. We found that all investigated index tests had relatively low sensitivities with high variability. In contrast, specificities were consistently and markedly higher than sensitivities across all tests. The standard bedside airway examination tests should be interpreted with caution, as they do not appear to be good screening tests. Among the tests we examined, the upper lip bite test showed the most favourable diagnostic test accuracy properties. Given the paucity of available data, future research is needed to develop tests with high sensitivities to make them useful, and to consider their use for screening difficult face mask ventilation and failed intubation. The 27 studies in 'Studies awaiting classification' may alter the conclusions of the review, once we have assessed them.

Background: Outcome is generally poor in out of hospital cardiac arrests (OHCA) with initial non-shockable rhythms. Termination of resuscitation rules facilitate early prognostication at the scene to cease resuscitation attempts in futile situations and to proceed advanced life support in promising conditions. As pulseless electrical activity (PEA) is present as first rhythm in every 4th OHCA we were interested if the initial electrical frequency in PEA predicts survival., Methods: All patients >18 years of age with non-traumatic OHCA and PEA as first rhythm between August 2013 and August 2015 from the Vienna Cardiac Arrest Registry were included in this retrospective observational study. Defibrillator and epidemiological data from the emergency medical system as survival data were processed considering the initial electrical activity in PEA and 30 days survival., Results: Out of 2149 OHCA patients, a total of 504 PEA patients were eligible for analyses. These patients were stratified into 4 groups according the initial electrical frequency in PEA: 10-24/min, 25-39/min, 40-59/min, >60/min. Compared to a frequency >60/min all other subgroups were associated with higher mortality especially those with an initial electrical frequency 10-24 (adjusted OR 0.56 (0.39-0.79) p = .001 for each category chance). QRS duration in PEA did not influence outcome. Patients in the >60/min group showed a 30-days-survival rate of 22% and a good neurological outcome in 15% of all patients - comparable to shockable cardiac arrest rhythms., Conclusion: Regardless of other resuscitation factors, higher initial electrical frequency in PEA is associated with increased odds of survival and good neurological outcome., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Catheter-related infections and dysfunction are the main catheter complications causing morbidity and mortality in hemodialysis patients. However, there are no consistent data for the choice of catheter lock solutions for tunneled hemodialysis lines. In this prospective, multicenter, randomized, controlled trial, two lock regimens using three commercial catheter lock solutions were compared in 106 hemodialysis patients with a newly inserted tunneled central catheter. In the taurolidine group, TauroLock™-Hep500 was used twice per week and TauroLock™-U25,000 once a week. In the citrate group, a four percent citrate solution was used after each dialysis. Both groups were compared regarding catheter-related infections, catheter dysfunction, and costs. Over a period of 15,690 catheter days, six catheter-related infections occurred in six of 52 patients in the taurolidine group, but 18 occurred in 13 of 54 patients in the citrate group, corresponding to 0.67 and 2.7 episodes of catheter-related infections per 1000 catheter days, respectively (Incidence Rate Ratio 0.25, 95% confidence interval, 0.09 to 0.63). Catheter dysfunction rates were significantly lower in the taurolidine group (18.7 vs. 44.3/1000 catheter days) and alteplase rescue significantly more frequent in the citrate group (9.8 vs. 3.8/1000 catheter days). These differences provided significant catheter-related cost savings of 43% in the taurolidine group vs. citrate group when overall expenses per patient and year were compared. Thus, use of taurolidine-based catheter lock solutions containing heparin and urokinase significantly reduced complications related to tunneled hemodialysis catheters when compared to four percent citrate solution and was overall more cost-efficient., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Aim of the Study: Current guidelines recommend targeted temperature management to improve neurological outcome after cardiac arrest. Evidence regarding an ideal sedative/analgesic regimen including skeletal muscle paralysis is limited., Methods: Patients were randomized to either a continuous administration of rocuronium (continuous-NMB-group) or to a continuous administration of saline supplemented by rocuronium bolus administration if demanded (bolus-NMB-group). The primary outcome was the number of shivering episodes. Secondary outcomes included survival and neurological status one year after cardiac arrest, time to awakening, length of stay as well as required cumulative dose of rocuronium, midazolam and fentanyl., Results: Sixty-three patients (32 continuous-NMB-group; 31 bolus-NMB-group) were enrolled. Differences in baseline characteristics were not significant. Shivering episodes were detected in 94% of the patients in the bolus-NMB-group compared to 25% of the patients receiving continuous rocuronium infusion (p<0.01). The continuous-NMB-group received significant lower doses of midazolam (4.3±0.8mg/kg vs. 5.1±0.9mg/kg, p<0.01) and fentanyl (62±14μg/kg vs. 71±7μg/kg, p<0.01), but higher cumulative doses of rocuronium (7.8±1.8mg/kg vs. 2.3±1.6mg/kg, p<0.01). Earlier awakening (2 [IQR 2;3] vs. 4 [IQR 2;7.5] days, p=0.04) and decreased length of stay at the ICU (6 [IQR 3;5.9] vs. 10 [IQR 5;15] days, p=0.03) were observed in the continuous-NMB-group. There were no significant differences in survival and quality of life 12 months after cardiac arrest., Conclusions: Continuous neuromuscular blockade during the first day after resuscitation reduced shivering, midazolam and fentanyl requirement, time to awakening and discharge from intensive care unit. There were no differences in overall survival, cooling rate and time to target temperature., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The significance of antibodies directed against paternal epitopes in the context of obstetric disorders is discussed controversially. In this study anti-HLA and anti-MIC-A antibodies were analysed in sera of women with uneventful pregnancy (n = 101), preeclampsia (PE, n = 55) and gestational diabetes (GDM, n = 36) using antigen specific microbeads. While two thirds of the women with uneventful pregnancy or GDM were HLA and MIC-A antibody positive in gestational week 11 to 13 with a modest increase towards the end of pregnancy, women with PE showed an inverse kinetic: 90% were HLA antibody positive in gestational week 11 to 13 and only 10% showed HLA reactivities at the end of the pregnancy. HLA antibody binding strength was more pronounced in gestational week 14 to 17 in patients with PE compared to women with uneventful pregnancy (maximum median fluorescence intensity of the highest ranked positive bead 7403, IQR 2193-7938 vs. 1093, IQR 395-5689; p = 0.04) and was able to predict PE with an AUC of 0.80 (95% CI 0.67-0.93; p = 0.002). Our data suggest a pathophysiological involvement of HLA antibodies in PE. HLA antibody quantification in early pregnancy may provide a useful tool to increase diagnostic awareness in women prone to develop PE.

Background: Organ failure increases mortality in patients with liver cirrhosis. Data about resuscitated cardiac arrest patients with liver cirrhosis are missing. This study aims to assess aetiology, survival and functional outcome in patients after successful cardiopulmonary resuscitation (CPR) with and without liver cirrhosis., Methods: Analysis of prospectively collected cardiac arrest registry data of consecutively hospital-admitted patients following successful CPR was performed. Patient's characteristics, admission diagnosis, severity of disease, course of disease, short- and long-term mortality as well as functional outcome were assessed and compared between patients with and without cirrhosis., Results: Out of 1068 patients with successful CPR, 47 (4%) had liver cirrhosis. Acute-on-chronic liver failure (ACLF) was present in 33 (70%) of these patients on admission, and four patients developed ACLF during follow-up. Mortality at 1 year was more than threefold increased in patients with liver cirrhosis (OR 3.25; 95% CI 1.33-7.96). Liver cirrhosis was associated with impaired neurological outcome (OR for a favourable cerebral performance category: 0.13; 95% CI 0.04-0.36). None of the patients with Child-Turcotte-Pugh (CTP) C cirrhosis survived 28 days with good neurological outcome. Overall nine (19%) patients with cirrhosis survived 28 days with good neurological outcome. All patients with ACLF grade 3 died within 28 days., Conclusion: Cardiac arrest survivors with cirrhosis have worse outcome than those without. Although one quarter of patients with liver cirrhosis survived longer than 28 days after successful CPR, patients with CTP C as well as advanced ACLF did not survive 28 days with good neurological outcome.

Background: Anaemia is a common problem experienced by critically-ill people. Treatment with erythropoiesis-stimulating agents (ESAs) has been used as a pharmacologic strategy when the blunted response of endogenous erythropoietin has been reported in critically-ill people. The use of ESAs becomes more important where adverse clinical outcomes of transfusing blood products is a limitation. However, this indication for ESAs is not licensed by regulatory authorities and is called off-label use. Recent studies concern the harm of ESAs in a critical care setting., Objectives: To focus on harms in assessing the effects of erythropoiesis-stimulating agents (ESAs), alone or in combination, compared with placebo, no treatment or a different active treatment regimen when administered off-label to critically-ill people., Search Methods: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO via OvidSP, CINAHL, all evidence-based medicine (EBM) reviews including IPA and SCI-Expanded, Conference Proceedings Citation Index- Science, BIOSIS Previews and TOXLINE up to February 2017. We also searched trials registries, checked reference lists of relevant studies and tracked their citations by using SciVerse Scopus., Selection Criteria: We considered randomized controlled trials (RCTs) and controlled observational studies, which compared scheduled systemic administration of ESAs versus other effective interventions, placebo or no treatment in critically-ill people., Data Collection and Analysis: Two review authors independently screened and evaluated the eligibility of retrieved records, extracted data and assessed the risks of bias and quality of the included studies. We resolved differences in opinion by consensus or by involving a third review author. We assessed the evidence using GRADE and created a 'Summary of findings' table. We used fixed-effect or random-effects models, depending on the heterogeneity between studies. We fitted three-level hierarchical Bayesian models to calculate overall treatment effect estimates., Main Results: Of the 27,865 records identified, 39 clinical trials and 14 observational studies, including a total of 945,240 participants, were eligible for inclusion. Five studies are awaiting classification. Overall, we found 114 adverse events in 33 studies (30 RCTs and three observational studies), and mortality was reported in 41 studies (32 RCTs and nine observational studies). Most studies were at low to moderate risk of bias for harms outcomes. However, overall harm assessment and reporting were of moderate to low quality in the RCTs, and of low quality in the observational studies. We downgraded the GRADE quality of evidence for venous thromboembolism and mortality to very low and low, respectively, because of risk of bias, high inconsistency, imprecision and limitations of study design.It is unclear whether there is an increase in the risk of any adverse events (Bayesian risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.21; 3099 participants; 9 studies; low-quality evidence) or venous thromboembolism (Bayesian RR 1.04, 95% CI 0.70 to 1.41; 18,917 participants; 18 studies; very low-quality evidence).There was a decreased risk of mortality with off-label use of ESAs in critically-ill people (Bayesian RR 0.76, 95% CI 0.61 to 0.92; 930,470 participants; 34 studies; low-quality evidence)., Authors' Conclusions: Low quality of evidence suggests that off-label use of ESAs may reduce mortality in a critical care setting. There was a lack of high-quality evidence about the harm of ESAs in critically-ill people. The information for biosimilar ESAs is less conclusive. Most studies neither evaluated ESAs' harm as a primary outcome nor predefined adverse events. Any further studies of ESA should address the quality of evaluating, recording and reporting of adverse events.

Introduction: The neutrophil lymphocyte ratio(NLR) is a marker of systemic inflammation. We hypothesized that admission NLR is related to mortality and that epinephrine application during resuscitation influences NLR in patients after successful resuscitation from out of hospital cardiac arrest (OHCA)., Methods: This retrospective cohort study is based on a registry including all OHCA patients who had a presumed cardiac cause of cardiac arrest and achieved sustained ROSC prior to admission between 2005 and 2014. Patients were categorized into three groups according to the calculated NLR at admission (NLR <6, ≥6, and 'abnormal differential' indicating no differential blood cell count on patients report due to exceedance of machine predefined parameter limits). The primary outcome measure was long-term mortality after OHCA. Cox proportional hazards models were used for multivariable analysis., Results: Out of 2273 OHCA patients during the study period a total of 1188(52%) patients were eligible for analysis, of those 274(23%) were female and mean age was 64 (25-75 IQR:52-72). Compared to a NLR<6 (n=442), adjusted hazard ratio for long-term mortality was significantly higher in patients with a NLR≥6 (n=447; 1.52 (95%CI 1.03-2.24)) and in patients with abnormal differential (n=299; 3.16 (95%CI 2.02-4.97)). Epinephrine application during resuscitation did not explain the effect of NLR on mortality., Conclusion: In this large retrospective cohort study of altogether >1000 OHCA patients, hospital admission NLR<6 compared to abnormal differential or NLR≥6 was associated with mortality independently from epinephrine application., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Mild therapeutic hypothermia is argued being beneficial for outcome after cardiac arrest., Materials and Methods: Retrospective analysis of Circulation Improving Resuscitation Care (CIRC) trial data to assess if therapeutic cooling to 33 ± 1 °C core temperature had an association with survival. Of 4231 adult, out-of-hospital cardiac arrests of presumed cardiac origin initially enrolled, eligibility criteria for therapeutic hypothermia were met by 1812. Logistic regression was undertaken in a stepwise fashion to account for the impact on outcome of each significant difference and for the variable of interest between the groups., Results: Out-of- and in-hospital cooled were 263 (15%), only after admission cooled were 230 (13%) and not cooled were 357 (20%) patients. The group cooled out of- and in hospital had 98 (37%) survivors as compared to the groups cooled in hospital only [80 (35%)] and of those not cooled [68 (19%)]. After adjusting for known covariates (sex, age, witnessed cardiac arrest, no- and low-flow time, shockable initial rhythm, random allocation, bystander cardiopulmonary resuscitation and percutaneous coronary intervention), the odds ratio for survival comparing no cooling to out-of- plus in-hospital cooling was 0·53 [95% confidence interval (CI): 0·46-0·61, P < 0·001], and comparing to in-hospital cooling only was 0·67 (95% CI: 0·50-0·89, P = 0·006)., Conclusion: Mild therapeutic hypothermia initiated out of hospital and/or in hospital was associated with improved survival within this secondary analysis of the CIRC cohort compared to no therapeutic hypothermia., (© 2017 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Recently, diffuse peritubular capillaritis (ptc) has been suggested to independently predict chronic transplant injury and loss, and although the ptc score is a diagnostic criterion for antibody-mediated rejection, the utility of diffuse ptc is under debate., Methods: We evaluated the diagnostic value of ptc characteristics in this cross-sectional study including 85 biopsies of patients with donor-specific antibodies (DSA). Biopsies were reevaluated for the extent (diffuse vs focal), score and leukocytic composition in relation to DSA binding strength (mean fluorescence intensity [MFI]&#95;max). Chronic allograft injury (transplant chronic glomerulopathy [cg] or chronic lesion score CLS]) were associated with ptc features., Results: Peritubular capillaritis was detected in 50% (76% mononuclear ptc). Peritubular capillaritis scores 1, 2, and 3 were present in 36%, 55%, and 9%, and focal or diffuse ptc in 36% or 64%. Diffuse ptc was associated with DSA MFI&#95;max (median: 4407 vs 2419 [focal ptc; P = 0.04] or 1946 [no ptc; P = 0.004]), cg (58% vs no ptc 24% [P = 0.02]), and higher CLS (mean: 6.81 vs 4.67 [focal ptc, P = 0.01] or 5.18 [no ptc, P = 0.001]), respectively. The association of ptc score of 2 or greater with cg was slightly better than with diffuse ptc. Diffuse ptc and ptc score of 2 or greater remained independently related to cg after adjusting for DSA&#95;MFI&#95;max, C4d, or previous rejection episodes, however lost their independent relation after adjusting for total microcirculation scores. Diffuse ptc was the only ptc characteristic independently related to CLS., Conclusions: Our results emphasize the clinical relevance of reporting diffuse ptc, which may relate to DSA binding strength and potentially to chronic graft injury.

Background: Antibody-mediated rejection (AMR) represents one of the cardinal causes of late allograft loss after kidney transplantation, and there is great need for noninvasive tools improving early diagnosis of this rejection type. One promising strategy might be the quantification of peripheral blood DNA levels of the highly prevalent and apathogenic Torque Teno virus (TTV), which might mirror the overall level of immunosuppression and thus help determine the risk of alloimmune response., Methods: To assess the association between TTV load in the peripheral blood and AMR, 715 kidney transplant recipients (median, 6.3 years posttransplantation) were subjected to a systematical cross-sectional AMR screening and, in parallel, TTV quantification., Results: Eighty-six of these recipients had donor-specific antibodies and underwent protocol biopsy, AMR-positive patients (n = 46) showed only 25% of the TTV levels measured in patients without AMR (P = 0.003). In a generalized linear model, higher TTV levels were associated with a decreased risk for AMR after adjustment for potential confounders (risk ratio 0.94 per TTV log level; 95% confidence interval 0.90-0.99; P = 0.02)., Conclusions: Future studies will have to clarify whether longitudinal assessment of TTV load might predict AMR risk and help guide the type and intensity of immunosuppression to prevent antibody-mediated graft injury., Competing Interests: The authors declare no conflicts of interest.

Objectives: The quality of telephone-assisted cardiopulmonary resuscitation (CPR) needs improvement. This study investigates whether a dispatchers' perception is an adequate measure of the actual quality of CPR provided by laypersons., Material and Methods: Individual participant data from 3 randomized simulation trials, with identical methodology but different interventions, were combined for this analysis. Professional dispatchers gave telephone assistance to laypersons, who each provided 10 minutes of CPR on a manikin. Dispatchers were requested to classify the quality of providers' CPR as adequate or inadequate. Based on actual readings from manikins we classified providers' performance as adequate at 5-6 cm for depth and 100-120 compressions per minute (cpm) for rate. We calculated metrics of dispatcher accuracy., Results: Six dispatchers rated the performance of 94 laypersons (38 women [42%]) with a mean (SD) age of 37 (14) years. In 905 analyzed minutes of telephone-assisted CPR, the mean compression depth and rate was 41 (13) mm and 98 (24) cpm, respectively. Analysis of dispatchers' diagnostic test accuracy for adequate compression depth yielded a sensitivity of 65% (95 CI 36%-95%) and specificity of 42% (95% CI, 32%-53%). Analysis of their assessment of adequate compression rate yielded a sensitivity of 75% (95% CI, 64%-86%) and specificity of 42% (95% CI, 32%-52%). Although dispatchers always underestimated the actual values of CPR parameters, the female dispatchers evaluations were less inaccurate than the evaluations of make dispatchers; the dispatchers overall (males and females together) underestimated the adequacy of female laypersons' CPR performance to a greater degree than female dispatchers did., Conclusion: The ability of dispatchers to estimate the quality of telephone-assisted CPR is limited. Dispatchers estimates of CPR adequacy needs to be studied further in order to find ways that telephone-assisted CPR might be improved.

Aims: Ibutilide is a rapid-acting antiarrhythmic drug with worldwide use for conversion of recent-onset atrial fibrillation. Vernakalant, approved in the EU in 2010, is likewise used intravenously, with proven efficacy and safety compared with placebo and amiodarone in randomized clinical trials. The aim of our study was to compare the time to conversion and the conversion rate within 90 min in patients with recent-onset atrial fibrillation treated with vernakalant or ibutilide., Methods and Results: A randomized controlled trial registered at clinicaltrials.gov (NCT01447862) was performed in 100 patients with recent-onset atrial fibrillation treated at the emergency department of a tertiary care hospital. Patients received up to two short infusions of vernakalant (n = 49; 3 mg/kg followed by 2 mg/kg if necessary) or ibutilide (n = 51; 1 mg followed by another 1 mg if necessary) according to the manufacturer's instructions. Clinical and laboratory variables, adverse events, conversion rates, and time to conversion were recorded. Time to conversion of AF to sinus rhythm was significantly shorter in the vernakalant group compared with the ibutilide group (median time: 10 vs. 26 min, P = 0.01), and likewise the conversion success within 90 min was significantly higher in the vernakalant group (69 vs. 43%, log-rank P = 0.002). No serious adverse events occurred., Conclusion: Vernakalant was superior to ibutilide in converting recent-onset atrial fibrillation to sinus rhythm in the emergency department setting.

Objective: Mortality is frequently used as an outcome in critical care trials, being a patient-orientated variable and robust against information/selection bias. Mortality frequency, however, should be measured at a defined time point of follow-up. Practice of meta-analysis shows that follow-up times of trials in critical care medicine differ substantially. This may have substantial implications on potential pooling of effect estimates. We aimed to describe the current practice of mortality follow-up time definitions in a representative sample of published critical care randomized controlled trials and to analyze the influence of different follow-up times on subsequently pooled effect estimates., Data Sources: Cochrane CENTRAL, EMBASE, MEDLINE, PASCAL Biomed, and PsycINFO., Study Selection: Databases were searched for critical care randomized controlled trials published after 2000. A random sample of 50% was drawn for further review., Data Extraction: Study characteristics were extracted, as well as the number and time points of mortality ascertainment. Additional data were extracted from Kaplan-Meier plots, as available., Data Synthesis: Meta-regression and multilevel mixed-effects linear regression were used to analyze the influence of follow-up time (independent variable) on deviation of pooled risk ratios from study baseline (dependent variable). From 9,246 retrieved references, we included 106 studies representing 63,713 participants. Among these, 45 studies (43%) reported more than one time point, with 24 different time points at all, only three (28, 30, and 90 d) being reported in more than 10% of studies. Limiting meta-analyses to only one predefined time point would reduce the number of eligible studies by at least 60%. No influence of time points on meta-analytic summary effect estimates was found., Conclusions: In a large sample of critical care randomized controlled trials, numerous different mortality time points are reported. Mortality time points did not influence pooled point estimates of the effects. Consequently, it seems possible to pool effect estimates, which in turn will increase the precision of these effect estimates.

Cerebral metabolic alterations during cardiac arrest, cardiopulmonary resuscitation (CPR) and extracorporeal cardiopulmonary life support (ECLS) are poorly explored. Markers are needed for a more personalized resuscitation and post-resuscitation care. Aim of this study was to investigate early metabolic changes in the hippocampal CA1 region during ventricular fibrillation cardiac arrest (VF-CA) and ECLS versus conventional CPR. Male Sprague-Dawley rats (350g) underwent 8min untreated VF-CA followed by ECLS (n = 8; bloodflow 100ml/kg), mechanical CPR (n = 18; 200/min) until return of spontaneous circulation (ROSC). Shams (n = 2) were included. Glucose, glutamate and lactate/pyruvate ratio were compared between treatment groups and animals with and without ROSC. Ten animals (39%) achieved ROSC (ECLS 5/8 vs. CPR 5/18; OR 4,3;CI:0.7-25;p = 0.189). During VF-CA central nervous glucose decreased (0.32±0.1mmol/l to 0.04±0.01mmol/l; p<0.001) and showed a significant rise (0.53±0.1;p<0.001) after resuscitation. Lactate/pyruvate (L/P) ratio showed a 5fold increase (31 to 164; p<0.001; maximum 8min post ROSC). Glutamate showed a 3.5-fold increase to (2.06±1.5 to 7.12±5.1μmol/L; p<0.001) after CA. All parameters normalized after ROSC with no significant differences between ECLS and CPR. Metabolic changes during ischemia and resuscitation can be displayed by cerebral microdialysis in our VF-CA CPR and ECLS rat model. We found similar microdialysate concentrations and patterns of normalization in both resuscitation methods used. Institutional Protocol Number: GZ0064.11/3b/2011.

Background: Targeted temperature management (also known under 'therapeutic hypothermia', 'induced hypothermia'", or 'cooling') has been shown to be beneficial for neurological outcome in patients who have had successful resuscitation from sudden cardiac arrest, but it remains unclear when this intervention should be initiated., Objectives: To assess the effects of pre-hospital initiation of cooling on survival and neurological outcome in comparison to in-hospital initiation of cooling for adults with pre-hospital cardiac arrest., Search Methods: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, BIOSIS, and three trials registers from inception to 5 March 2015, and carried out reference checking, citation searching, and contact with study authors to identify additional studies., Selection Criteria: We searched for randomized controlled trials (RCTs) in adults with out-of-hospital cardiac arrest comparing cooling in the pre-hospital setting to in-hospital cooling. Our primary outcomes were survival and neurological outcome; our secondary outcomes were adverse events, quality of life, and length of stay in the intensive care unit (ICU) and in the hospital., Data Collection and Analysis: We used Cochrane's standard methodological procedures., Main Results: We included seven RCTs (2369 participants randomized) on the induction of pre-hospital cooling in comparison to in-hospital cooling. There was considerable methodological heterogeneity and risk of bias mainly due to deficits in the administration of cooling, therefore we refrained from pooling the results for survival and neurological outcome and we presented the results for each study separately. Adverse events were rare: based on four studies with 1713 adults pre-hospital induction of cooling may increase the risk of cardiac re-arrests. Risk of bias within the seven individual studies was generally moderate. Overall the quality of the evidence was very low. This was mainly driven by inconsistency and low precision., Authors' Conclusions: Currently, there is no convincing evidence to clearly delineate beneficial or harmful effects of pre-hospital induction of cooling in comparison to in-hospital induction of cooling. This conclusion is based on very low quality evidence.

Background: Initial goal-directed resuscitation for hypotensive shock usually includes administration of intravenous fluids, followed by initiation of vasopressors. Despite obvious immediate effects of vasopressors on haemodynamics, their effect on patient-relevant outcomes remains controversial. This review was published originally in 2004 and was updated in 2011 and again in 2016., Objectives: Our objective was to compare the effect of one vasopressor regimen (vasopressor alone, or in combination) versus another vasopressor regimen on mortality in critically ill participants with shock. We further aimed to investigate effects on other patient-relevant outcomes and to assess the influence of bias on the robustness of our effect estimates., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 Issue 6), MEDLINE, EMBASE, PASCAL BioMed, CINAHL, BIOSIS and PsycINFO (from inception to June 2015). We performed the original search in November 2003. We also asked experts in the field and searched meta-registries to identify ongoing trials., Selection Criteria: Randomized controlled trials (RCTs) comparing various vasopressor regimens for hypotensive shock., Data Collection and Analysis: Two review authors abstracted data independently. They discussed disagreements between them and resolved differences by consulting with a third review author. We used a random-effects model to combine quantitative data., Main Results: We identified 28 RCTs (3497 participants) with 1773 mortality outcomes. Six different vasopressors, given alone or in combination, were studied in 12 different comparisons.All 28 studies reported mortality outcomes; 12 studies reported length of stay. Investigators reported other morbidity outcomes in a variable and heterogeneous way. No data were available on quality of life nor on anxiety and depression outcomes. We classified 11 studies as having low risk of bias for the primary outcome of mortality; only four studies fulfilled all trial quality criteria.In summary, researchers reported no differences in total mortality in any comparisons of different vasopressors or combinations in any of the pre-defined analyses (evidence quality ranging from high to very low). More arrhythmias were observed in participants treated with dopamine than in those treated with norepinephrine (high-quality evidence). These findings were consistent among the few large studies and among studies with different levels of within-study bias risk., Authors' Conclusions: We found no evidence of substantial differences in total mortality between several vasopressors. Dopamine increases the risk of arrhythmia compared with norepinephrine and might increase mortality. Otherwise, evidence of any other differences between any of the six vasopressors examined is insufficient. We identified low risk of bias and high-quality evidence for the comparison of norepinephrine versus dopamine and moderate to very low-quality evidence for all other comparisons, mainly because single comparisons occasionally were based on only a few participants. Increasing evidence indicates that the treatment goals most often employed are of limited clinical value. Our findings suggest that major changes in clinical practice are not needed, but that selection of vasopressors could be better individualised and could be based on clinical variables reflecting hypoperfusion.

Background: Good neurological outcome after cardiac arrest is difficult to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and several clinical studies on this topic have been published. This review was originally published in 2009; updated versions were published in 2012 and 2016., Objectives: We aimed to perform a systematic review and meta-analysis to assess the influence of therapeutic hypothermia after cardiac arrest on neurological outcome, survival and adverse events., Search Methods: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10); MEDLINE (1971 to May 2015); EMBASE (1987 to May 2015); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1988 to May 2015); and BIOSIS (1989 to May 2015). We contacted experts in the field to ask for information on ongoing, unpublished or published trials on this topic.The original search was performed in January 2007., Selection Criteria: We included all randomized controlled trials (RCTs) conducted to assess the effectiveness of therapeutic hypothermia in participants after cardiac arrest, without language restrictions. We restricted studies to adult populations cooled by any cooling method, applied within six hours of cardiac arrest., Data Collection and Analysis: We entered validity measures, interventions, outcomes and additional baseline variables into a database. Meta-analysis was performed only for a subset of comparable studies with negligible heterogeneity. We assessed the quality of the evidence by using standard methodological procedures as expected by Cochrane and incorporated the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach., Main Results: We found six RCTs (1412 participants overall) conducted to evaluate the effects of therapeutic hypothermia - five on neurological outcome and survival, one on only neurological outcome. The quality of the included studies was generally moderate, and risk of bias was low in three out of six studies. When we compared conventional cooling methods versus no cooling (four trials; 437 participants), we found that participants in the conventional cooling group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.18 to 3.21). The quality of the evidence was moderate.Across all studies that used conventional cooling methods rather than no cooling (three studies; 383 participants), we found a 30% survival benefit (RR 1.32, 95% CI 1.10 to 1.65). The quality of the evidence was moderate.Across all studies, the incidence of pneumonia (RR 1.15, 95% CI 1.02 to 1.30; two trials; 1205 participants) and hypokalaemia (RR 1.38, 95% CI 1.03 to 1.84; two trials; 975 participants) was slightly increased among participants receiving therapeutic hypothermia, and we observed no significant differences in reported adverse events between hypothermia and control groups. Overall the quality of the evidence was moderate (pneumonia) to low (hypokalaemia)., Authors' Conclusions: Evidence of moderate quality suggests that conventional cooling methods provided to induce mild therapeutic hypothermia improve neurological outcome after cardiac arrest, specifically with better outcomes than occur with no temperature management. We obtained available evidence from studies in which the target temperature was 34°C or lower. This is consistent with current best medical practice as recommended by international resuscitation guidelines for hypothermia/targeted temperature management among survivors of cardiac arrest. We found insufficient evidence to show the effects of therapeutic hypothermia on participants with in-hospital cardiac arrest, asystole or non-cardiac causes of arrest.

Background: Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients., Methods: In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR)., Results: After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92) vs. 468.80 (414.27-488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106) vs. 0.083 (0.054-0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression., Conclusions: HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant recipients may benefit from a cyclosporine A-based immunosuppressive regimen., Trial Registration: ClinicalTrials.gov NCT02108301.

Background: Mild therapeutic hypothermia interferes with multiple cascades of the ischaemia/reperfusion injury that is known as primary mechanism for brain damage after cardiac arrest. First resuscitation attempts and the duration of resuscitation efforts will initiate and aggravate this pathophysiology. Therefore we investigated the interaction between the duration of basic and advanced life support and outcome after cardiac arrest in patients treated with or without mild therapeutic hypothermia., Methods: This retrospective cohort study included patients 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest with presumed cardiac cause, which remained comatose after restoration of spontaneous circulation. The basic and advanced life support 'low-flow' time, categorized into four quartiles (0-11, 12-17, 18-28, ≥ 29 min), was correlated with neurological outcome., Results: Out of 1103 patients 613 were cooled to a target temperature of 33 ± 1 °C for 24h. In the three quartiles with 'low-flow' time up to 28 min cooling was associated with >2-fold odds of favourable neurological outcome. In the fourth quartile with 'low-flow' time of ≥ 29 min cooling had no influence on neurological outcome (OR: 0.73; 95% CI: 0.38-1.4, test for interaction p<0.01)., Conclusion: The duration of resuscitation efforts, defined as 'low-flow' time, influences the effectiveness of mild therapeutic hypothermia in terms of neurologic outcome. Patients with low to moderate 'low-flow' time benefit most from this treatment., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Many patients visiting an emergency department are in reduced general condition of health and at risk of suffering further deterioration during their stay. We wanted to test the feasibility of a new monitoring system in a waiting area of an emergency department.In an observational cross-sectional single-center study, patients with acute cardiac or pulmonary symptoms or in potentially life-threatening conditions were enrolled. Monitoring devices providing vital signs via short range radio (SRR) at certain time points and compliance evaluation forms were used.Out of 230 patients, 4 wanted to terminate their participation prematurely. No data was lost due to technical difficulties. Over a median monitoring period of 178 (118-258) min per patient, 684 h of vital sign data were collected and used to assist managing those patients. Linear regression analysis between clinical symptom category groups of patients showed significant differences in the respiratory rate and noninvasive blood pressure courses. Feedback from patients and users via questionnaires showed overall very good acceptance and patients felt that they were given better care.To assist medical staff of an emergency department waiting area to rapidly response to potentially life-threatening situations of its patients, a new monitoring system proved to be feasible and safe.

Background: Clarithromycin, known as a potent inhibitor of the cytochrome P450 isoenzyme CYP3A, may increase the plasma concentration of statins metabolized by this pathway; therefore, increase the risk of interaction with statins in reference to pharmacokinetic studies. This study aimed to characterize whether the concomitant use of a statin with clarithromycin is associated with serious outcomes among adult persons., Methods: Health claims data of adult persons in the Regional Sickness Fund of Burgenland, Austria, who filled a prescription for clarithromycin between July 1, 2009 and June 30, 2012 were reviewed retrospectively. We assumed that the risk of hospitalisation increases acutely with the indication for taking an antibiotic, whereas statin use can be considered a chronic exposure with a low constant effect on hospitalisation. When defining the population as persons taking clarithromycin and the use of statins as the exposure we could achieve a comparable effect in both groups from the acute condition on hospitalisation. Therefore, we defined exposed patients as those who had overlapping treatment with a statin and unexposed controls as those who had filled a prescription for clarithromycin without concomitant statin therapy. Outcome was defined as a composite of hospital admission or death within 30 days after starting clarithromycin. We used generalised linear regression to model an association between outcome and exposure to statins., Results: Among 28,484 prescriptions of clarithromycin, 2317 persons were co-exposed to statins. Co-administration of CYP3A4 metabolized statins and clarithromycin was associated with a 2.11 fold increased risk of death or hospitalisation (95 % confidence interval [CI]: 1.79-2.48). This effect was explained by age, evidence of cardiovascular disease, diabetes mellitus and utilization of other antibiotics (multivariable adjusted risk ratio: 1.02, 95 % CI: 0.85-1.22). The sensitivity analyses did not change the significance of effect., Conclusions: The risk for hospitalisation or death in persons receiving clarithromycin increases with age and cardiovascular disease but is not causally associated with statin-clarithromycine co-administration.

Aims: Arterial hypertension is a well-established factor for increased risk of cardiovascular diseases, but low admission blood pressure has also been suggested as predictor for increased mortality. We hypothesised that in patients with acute myocardial infarction admission blood pressure at the Emergency Department predicts long-term mortality., Methods: We included consecutive patients treated for acute myocardial infarction (AMI) at our 2,200-bed tertiary care hospital from 1991 to 2009 into our cohort. Systolic, diastolic and pulse pressure on admission were analysed as main predictors for 1-year mortality. We adjusted for several baseline factors and tested for interactions using multivariable regression models., Results: We included 3943 patients among whom 3604 were alive after 1 year. With increasing admission blood pressure 1-year mortality risk decreased incrementally to a 70% reduced relative risk in the highest blood pressure categories vs. the lowest categories. This effect was independent of blood pressure modifying interventions., Conclusions: In acute myocardial infarction, admission blood pressure predicts long-term mortality in an inverse relation. With increasing admission blood pressure long-term mortality decreases. Low admission blood pressure should serve as a warning sign in patients with AMI. Admission blood pressure should therefore be interpreted in opposite to the regular, preventive, point of view., (© 2015 John Wiley & Sons Ltd.)

By the Banff classification, the score of peritubular capillaritis, its extent, and its cellular composition should normally be reported in renal allograft pathology. While the score represents an important diagnostic and prognostic variable, the clinical value of capillaritis extent or composition has yet to be resolved. In a retrospective study of 749 renal transplant recipients subjected to 1322 indication biopsies, we found that prevalence scores of 1, 2, or 3 in the biopsy specimens were 10.7, 11.6, and 2.6%, respectively. Focal and diffuse peritubular capillaritis (inflammation over 50% of cortical peritubular capillaries) was diagnosed in 10.5 or 14.4% of cases, respectively. Mononuclear, granulocytic, and mixed peritubular capillaritis was present in 13.1, 3.3, and 8.5%, respectively. While peritubular capillaritis without further subclassification was not related to higher allograft loss rates, a score of 3 (hazard ratio 2.57 (CI: 1.25-5.28)) and diffuse peritubular capillaritis (1.67 (1.1-2.54)) were significant impartial risk factors for allograft loss. Diffuse peritubular capillaritis was independently associated with features of chronic antibody-mediated rejection and greater eGFR decline after 3 years. In contrast, detailed report of leukocytic composition in peritubular capillaritis did not confer additional prognostic information. Thus, in contrast to typing the infiltrating inflammatory cells, the score and extent of peritubular capillaritis in kidney allograft pathology is essential to assess transplant prognosis.

Background: Ventilation is still one key element of advanced life support. Emergency medical technicians (EMTs) without training in advanced airway management usually use bag valve mask ventilation (BVM). Bag valve mask ventilation requires proper training and yet may be difficult and ineffective. Supraglottic airway devices, such as the laryngeal tube (LT), have been proposed as alternatives. Safety and feasibility are unclear if used by EMTs with limited training only. We compared efficacy of the LT to BVM for out-of-hospital cardiac arrest in a primarily volunteer-based emergency medical services., Methods: This is a prospective multicenter observational cohort study. We compared safety (injuries and regurgitation) and feasibility (successful ventilation) in patients who received BVM, LT, or fallback to BVM after LT and controlled for potential confounders using logistic regression., Results: A total of 517 cases were documented, 395 (76.7%) with LT, 74 (14.4%) with BVM, and 48 (9.3%) where EMTs fell back from LT to BVM. There was no difference between groups regarding demographics (71 ± 17 years; 37% female) and initial rhythm (44% shockable). Placement of LT at first attempt was possible in 300 cases (76%), and at second attempt, in 91 cases (23%). Compared to BVM (22 cases [30%]), ventilation was more frequently successful with LT in 367 cases (93%; adjusted risk ratio, 3.1 [95% confidence interval, 1.3-7.1]; P < .01) and less successful with LT to BVM in 7 cases (15%; 0.3 [0.1-0.7]; P = .01). Five injuries (1.3%) were documented. Regurgitation was observed 8 (11%), 22 (6%; P < .01), and 8 times (17%; P < .01), respectively., Conclusions: Use of the LT during out-of-hospital cardiac arrest by EMTs with only basic training appears safe and feasible. Compared to BVM, success rates were higher. Injuries were relatively rare., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Current management guidelines of HIV infected adults include recommendation to immunization against common vaccine preventable diseases. This effort is hindered by the scarce knowledge regarding the immunization status of this especially vulnerable patient group. This study analyzed the serostatus for pertussis, diphtheria and tetanus of more than 700 HIV infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seropositivity was 84% for diphtheria, 51% for tetanus and 1% for pertussis. Migrants had a lower chance of tetanus seropositivity (OR 0.30 (CI 0.21 to 0.43)). Increase in CDC classification were associated with increased diphtheria seropositivity (OR 1.42 (CI 1.02 to 1.98)) and a CD4 nadir<200c/μl was associated with increased pertussis seropositivity (OR 12.2, 95% CI 1.2 to 121). Importantly due to the well preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. In patients with a CD4 count>200c/μl, 95% lacked seroprotection to at least one of the antigens included in the triple vaccine Tdap and could be vaccinated. Thus, a proactive approach would largely reduce the number of patients at risk for these vaccine-preventable diseases., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Autosomal-dominant polycystic kidney disease (ADPKD) is a hereditary illness that causes renal tubular epithelial cells to form cysts that proliferate and destroy renal tissue. This usually leads to a decline in renal function, and often to terminal kidney failure, with need for renal replacement therapy. There is currently no causative therapy. The mammalian target of rapamycin (mTOR) inhibitor sirolimus (SIR) is an immunosuppressant with strong antiproliferative effects, and is potentially able to stop or reduce cyst growth and preserve renal function in ADPKD. Continuous mTOR exposure results in a loss of its antiproliferative effects on renal tubular cells. With a half-life of roughly 60 hours, pulsed (weekly) administration of SIR may be an effective way to reduce cyst growth and preserve excretory renal function in ADPKD., Methods/design: The Vienna RAP Study is a randomized, double-blind, placebo-controlled trial, funded by the Anniversary Fund of the Oesterreichische Nationalbank. We will investigate the effects of a weekly dose of 3 mg SIR on kidney function in 34 patients with advanced ADPKD, compared to a placebo equivalent in 34 patients with advanced ADPKD, over 24 months. The primary endpoint is creatinine level (less or equal than 1.5-fold increase in serum creatinine without initiation of dialysis over two years) and dialysis, renal transplantation, or death. The secondary endpoints are safety, change in proteinuria (as indicated by albumin/creatinine- and protein/creatinine ratio, respectively), and creatinine clearance., Discussions: The Vienna RAP Study is, to the best of our knowledge, the first study to investigate the effects of a pulsed (weekly) dose of SIR on renal function in ADPKD., Trial Registration: This trial was registered with EudraCT (identifier: 2012-000550-60 (EU)) on 27 November 2013 and with ClinicalTrials.gov (identifier: NCT02055079 (USA)) on 3 February 2014.

Background: In CPR, sufficient compression depth is essential. The American Heart Association ("at least 5cm", AHA-R) and the European Resuscitation Council ("at least 5cm, but not to exceed 6cm", ERC-R) recommendations differ, and both are hardly achieved. This study aims to investigate the effects of differing target depth instructions on compression depth performances of professional and lay-rescuers., Methods: 110 professional-rescuers and 110 lay-rescuers were randomized (1:1, 4 groups) to estimate the AHA-R or ERC-R on a paper sheet (given horizontal axis) using a pencil and to perform chest compressions according to AHA-R or ERC-R on a manikin. Distance estimation and compression depth were the outcome variables., Results: Professional-rescuers estimated the distance according to AHA-R in 19/55 (34.5%) and to ERC-R in 20/55 (36.4%) cases (p=0.84). Professional-rescuers achieved correct compression depth according to AHA-R in 39/55 (70.9%) and to ERC-R in 36/55 (65.4%) cases (p=0.97). Lay-rescuers estimated the distance correctly according to AHA-R in 18/55 (32.7%) and to ERC-R in 20/55 (36.4%) cases (p=0.59). Lay-rescuers yielded correct compression depth according to AHA-R in 39/55 (70.9%) and to ERC-R in 26/55 (47.3%) cases (p=0.02)., Conclusion: Professional and lay-rescuers have severe difficulties in correctly estimating distance on a sheet of paper. Professional-rescuers are able to yield AHA-R and ERC-R targets likewise. In lay-rescuers AHA-R was associated with significantly higher success rates. The inability to estimate distance could explain the failure to appropriately perform chest compressions. For teaching lay-rescuers, the AHA-R with no upper limit of compression depth might be preferable., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with malignancies are at increased risk of serious influenza related complications with higher rates of hospitalization and mortality than healthy cohorts. Although annual vaccination against influenza infection is recommended, vaccination rates among cancer patients are apparently low. The reasons for the low compliance to influenza vaccine and the influenza vaccination rate among Austrian cancer patients have not been studied in detail yet., Patients and Methods: From July 1, 2013 to October 31, 2013, 444 patients treated in the outpatient departments of the Clinical Division of Oncology and the Clinical Division of Haematology and Haemostaseology of the General Hospital Vienna participated in a survey on different aspects of influenza vaccination., Results: In total, only 80 out of 444 patients (18%) had received influenza vaccination in the previous year. The influenza vaccination rate was higher amongst patients with haematological malignancies (22%) compared to patients with solid tumours (13%). Higher age was significantly associated with a higher probability for being vaccinated. Collecting information about influenza vaccination primarily from media or the internet was not significantly associated with influenza vaccination status. Information through a medical consultation or a recommendation by the attending physician resulted in significant higher influenza vaccination coverage rates. Only 199 out of the 444 patients (44.8%) were informed by a physician about influenza vaccination and only 18 out of 337 patients (5.3%) with a diagnosis of a malignant disease were informed by their treating oncologist. The main reasons for influenza vaccination denial were concerns about interaction with the malignant disease and potential side-effects., Conclusion: Information about influenza vaccination during a medical consultation and a clear recommendation by the attending physician are highly predictive for acceptance of influenza vaccination. Increased awareness among physicians, especially oncologists is of utmost importance to effectively improve IVR in patients with malignant disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Targeted temperature management improves outcome after cardiopulmonary resuscitation. Reduction of resting energy expenditure might be one mode of action. The aim of this study was to correlate resting energy expenditure and substrate oxidation rates with targeted temperature management at 33°C and outcome in patients after cardiac arrest., Methods: This prospective, observational cohort study was performed at the department of emergency medicine and a medical intensive care unit of a university hospital. Patients after successful cardiopulmonary resuscitation undergoing targeted temperature management at 33°C for 24 hours with subsequent rewarming to 36°C and standardized sedation, analgesic and paralytic medication were included. Indirect calorimetry was performed five times within 48 h after cardiac arrest. Measurements were correlated to outcome with repeated measures ANOVA, linear and logistic regression analysis., Results: In 25 patients resting energy expenditure decreased 20 (18 to 27) % at 33°C compared to 36°C without differences between outcome groups (favourable vs. unfavourable: 25 (21 to 26) vs. 21 (16 to 26); P = 0.5). In contrast to protein oxidation rate (favourable vs. unfavourable: 35 (11 to 68) g/day vs. 39 (7 to 75) g/day, P = 0.8) patients with favourable outcome had a significantly higher fat oxidation rate (139 (104 to 171) g/day vs. 117 (70 to 139) g/day, P <0.05) and a significantly lower glucose oxidation rate (30 (-34 to 88) g/day vs. 77 (19 to 138) g/day; P < 0.05) as compared to patients with unfavourable neurological outcome., Conclusions: Targeted temperature management at 33°C after cardiac arrest reduces resting energy expenditure by 20% compared to 36°C. Glucose and fat oxidation rates differ significantly between patients with favourable and unfavourable neurological outcome., Trial Registration: Clinicaltrials.gov NCT00500825. Registered 11 July 2007.

Objectives: We investigated the effect on compression rate and depth of a conventional metronome and a voice metronome in simulated telephone-assisted, protocol-driven bystander Cardiopulmonary resucitation (CPR) compared to standard instruction., Material and Methods: Thirty-six lay volunteers performed 10 minutes of compression-only CPR in a prospective, investigator-blinded, 3-arm study on a manikin. Participants were randomized either to standard instruction ("push down firmly, 5 cm"), a regular metronome pacing 110 beats per minute (bpm), or a voice metronome continuously prompting "deep-deepdeep- deeper" at 110 bpm. The primary outcome was deviation from the ideal chest compression target range (50 mm compression depth x 100 compressions per minute x 10 minutes = 50 m). Secondary outcomes were CPR quality measures (compression and leaning depth, rate, no-flow times) and participants' related physiological response (heart rate, blood pressure and nine hole peg test and borg scales score). We used a linear regression model to calculate effects., Results: The mean (SD) deviation from the ideal target range (50 m) was -11 (9) m in the standard group, -20 (11) m in the conventional metronome group (adjusted difference [95%, CI], 9.0 [1.2-17.5 m], P=.03), and -18 (9) m in the voice metronome group (adjusted difference, 7.2 [-0.9-15.3] m, P=.08). Secondary outcomes (CPR quality measures and physiological response of participants to CPR performance) showed no significant differences., Conclusion: Compared to standard instruction, the conventional metronome showed a significant negative effect on the chest compression target range. The voice metronome showed a non-significant negative effect and therefore cannot be recommended for regular use in telephone-assisted CPR.

Current guidelines recommend screening for HIV infected patients susceptible for vaccine preventable diseases and offering of immunization. However, data regarding the vaccination coverage among this group are largely missing. This study analyzed the serostatus for Measles, Mumps and Rubella of more than 700 HIV infected patients residing in Austria. These patients were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seronegativity was 8.4% for Measles, 33.4% for Mumps and 18.8% for Rubella. In total, out of the 713 HIV infected adults analyzed, almost half (47.8%) would require MMR vaccination. In a multivariate analysis migration was significantly associated with seronegativity for Measles (OR 0.5, CI 0.27-0.9) and Mumps (OR 0.57, CI 0.39-0.81). Importantly due to the well preserved immune status of nearly all participants vaccination would be feasible in the majority of the seronegative patients. Thus, a proactive approach would largely reduce the number of patients at risk for vaccine-preventable diseases., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aims: Carbon monoxide (CO) can cause lethal intoxication, but the burden of occult CO poisoning is still unclear. We aimed at prospectively assessing the number of patients with occult CO poisoning presenting to an emergency department within one year., Methods: Prospective, observational study according to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) statement for cross sectional studies at a European high volume tertiary-care emergency department., Results: Thirty-two thousand three-hundred and ninety-six consecutive patients whose vital signs were assessed at triage, regardless of their complaints. Active screening for CO-poisoning by non-invasive CO-oximetry was performed at triage. A pragmatic diagnosis of CO poisoning was made by attending physicians in 32 cases, representing 99/100,000 emergency department (ED)-patients. Three different definitions of poisoning were developed based on physicians' decision criteria, resulting in 9, 12, and 48 cases, respectively., Conclusions: In our study population, the prevalence of CO poisoning was twice as high as previously reported. The number of cases highly depends on the definition used, with more strict definitions excluding mainly cases during the summer months, where the source of CO often remains unknown. A clear consensus on which patients have to be regarded as 'poisoned' is urgently needed in order to allow comparison across studies., (© 2014 John Wiley & Sons Ltd.)

Background & Aims: Hepatopulmonary syndrome (HPS) occurs in 20-30% of patients with liver cirrhosis and is associated with a >2 fold increased mortality. Endothelial dysfunction seems to play a central role in its pathogenesis. von Willebrand factor antigen (vWF-Ag), an established marker of endothelial dysfunction, is significantly elevated in patients with liver cirrhosis, portal hypertension, and in experimental HPS. Aim of the present study was to evaluate the impact of vWF-Ag as a screening marker for presence of HPS in patients with stable cirrhosis., Methods: 145 patients with stable liver cirrhosis were screened for presence of HPS in this prospective cohort type cross sectional diagnostic study. vWF-Ag and SaO2 levels were assessed at time of screening for HPS. Criteria of HPS were fulfilled in 31 (21%) patients., Results: vWF-Ag levels were significantly higher in patients with HPS compared to patients without HPS (p<0.001). Furthermore, vWF-Ag correlated significantly with gas exchange in HPS positive patients (p<0.05). vWF-Ag is an independent predictor of HPS after correction for sex, age, model for endstage-liver disease (MELD), and hepatic venous pressure gradient (HVPG) (OR per 1% increase of vWF-Ag: 1.02, 95% CI: 1.00-1.04, p<0.05). The best cut-off was 328% at a sensitivity of 100% and specificity of 53.5%; positive predictive value: 36.9%; negative predictive value: 100%., Conclusions: HPS is associated with elevated vWF-Ag levels. vWF-Ag may be a useful screening tool for early detection of HPS. Further studies investigating vWF-Ag in HPS will be needed to confirm our findings., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)