Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: a systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis to evaluate the impact of extracorporeal carbon dioxide removal (ECCO2R) on gas exchange and respiratory settings in critically ill adults with respiratory failure. METHODS: We conducted a comprehensive database search, including observational studies and randomized controlled trials (RCTs) from January 2000 to March 2022, targeting adult ICU patients undergoing ECCO2R. Primary outcomes were changes in gas exchange and ventilator settings 24 h after ECCO2R initiation, estimated as mean of differences, or proportions for adverse events (AEs); with subgroup analyses for disease indication and technology. Across RCTs, we assessed mortality, length of stay, ventilation days, and AEs as mean differences or odds ratios. RESULTS: A total of 49 studies encompassing 1672 patients were included. ECCO2R was associated with a significant decrease in PaCO2, plateau pressure, and tidal volume and an increase in pH across all patient groups, at an overall 19% adverse event rate. In ARDS and lung transplant patients, the PaO2/FiO2 ratio increased significantly while ventilator settings were variable. "Higher extraction" systems reduced PaCO2 and respiratory rate more efficiently. The three available RCTs did not demonstrate an effect on mortality, but a significantly longer ICU and hospital stay associated with ECCO2R. CONCLUSIONS: ECCO2R effectively reduces PaCO2 and acidosis allowing for less invasive ventilation. "Higher extraction" systems may be more efficient to achieve this goal. However, as RCTs have not shown a mortality benefit but increase AEs, ECCO2R's effects on clinical outcome remain unclear. Future studies should target patient groups that may benefit from ECCO2R. PROSPERO Registration No: CRD 42020154110 (on January 24, 2021).

Drone-Facilitated Real-Time Video-Guided Feedback Helps to Improve the Quality of Lay Bystander Basic Life Support. A Randomized Controlled Simulation Trial.

OBJECTIVES: Telephone instructions are commonly used to improve cardiopulmonary resuscitation (CPR) by lay bystanders. This usually implies an audio but no visual connection between the provider and the emergency medical telecommunicator. We aimed to investigate whether video-guided feedback via a camera drone enhances the quality of CPR. METHODS: We conducted a randomized controlled simulation trial. Lay rescuers performed 8 min of CPR on an objective feedback manikin. Participants were randomized to receive telephone instructions with (intervention group) or without (control group) a drone providing a visual connection with the telecommunicator after a 2-min run-in phase. Performed work (total compression depth minus total lean depth) was the primary outcome. Secondary outcomes were the proportion of effective chest compressions, average compression depth, subjective physical strain measured every 2 min, and dexterity in the nine-hole peg test after the scenario. Outcomes were compared using the t- and Mann Whitney-U tests. A two-sided p-value of <0.05 was considered significant. RESULTS: We included 27 individuals (14 (52%) female, mean age 41 ± 14 years). Performed work was greater in the intervention than in the control group (41.3 ± 7.0 vs. 33.9 ± 10.9 m; absolute difference 7.5, 95% CI 1.4 to 14.8; p = 0.046), with higher average compression depth (49 ± 7 vs. 40 ± 13 mm; p = 0.041), and higher proportions of adequate chest compressions (43 (IQR 14-60) vs. 3 (0-29) %; p = 0.041). We did not find any significant differences regarding the remaining secondary outcomes. CONCLUSION: Video-guided feedback via drones might be a helpful tool to enhance the quality of telephone-assisted CPR in lay bystanders.

Hypothermia for neuroprotection in adults after cardiac arrest.

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 for a favourable prognosis. 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: To evaluate the benefits and harms of therapeutic hypothermia after cardiac arrest in adults compared to standard treatment. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 30 September 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults comparing therapeutic hypothermia after cardiac arrest with standard treatment (control). We included studies with adults cooled by any method, applied within six hours of cardiac arrest, to target body temperatures of 32 °C to 34 °C. Good neurological outcome was defined as no or only minor brain damage allowing people to live an independent life. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome was 1. neurological recovery. Our secondary outcomes were 2. survival to hospital discharge, 3. quality of life, 4. cost-effectiveness and 5. ADVERSE EVENTS: We used GRADE to assess certainty. MAIN RESULTS: We found 12 studies with 3956 participants reporting the effects of therapeutic hypothermia on neurological outcome or survival. There were some concerns about the quality of all the studies, and two studies had high risk of bias overall. When we compared conventional cooling methods versus any type of standard treatment (including a body temperature of 36 °C), we found that participants in the therapeutic hypothermia group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.41, 95% confidence interval (CI) 1.12 to 1.76; 11 studies, 3914 participants). The certainty of the evidence was low. When we compared therapeutic hypothermia with fever prevention or no cooling, we found that participants in the therapeutic hypothermia group were more likely to reach a favourable neurological outcome (RR 1.60, 95% CI 1.15 to 2.23; 8 studies, 2870 participants). The certainty of the evidence was low. When we compared therapeutic hypothermia methods with temperature management at 36 °C, there was no evidence of a difference between groups (RR 1.78, 95% CI 0.70 to 4.53; 3 studies; 1044 participants). The certainty of the evidence was low. Across all studies, the incidence of pneumonia, hypokalaemia and severe arrhythmia was increased amongst participants receiving therapeutic hypothermia (pneumonia: RR 1.09, 95% CI 1.00 to 1.18; 4 trials, 3634 participants; hypokalaemia: RR 1.38, 95% CI 1.03 to 1.84; 2 trials, 975 participants; severe arrhythmia: RR 1.40, 95% CI 1.19 to 1.64; 3 trials, 2163 participants). The certainty of the evidence was low (pneumonia, severe arrhythmia) to very low (hypokalaemia). There were no differences in other reported adverse events between groups. AUTHORS' CONCLUSIONS: Current evidence suggests that conventional cooling methods to induce therapeutic hypothermia may improve neurological outcomes after cardiac arrest. We obtained available evidence from studies in which the target temperature was 32 °C to 34 °C.

Add-On Prostaglandin E1 in Venovenous Extracorporeal Membrane Oxygenation: A Randomized, Double-Blind, Placebo-controlled Pilot Trial.

Rationale: Prostaglandin E1 (alprostadil; PGE1), in addition to low-dose unfractionated heparin, increases the biocompatibility of extracorporeal systems and enhances the efficacy of artificial organs without increasing bleeding risk. Objectives: We investigated the safety and efficacy of PGE1 in adults receiving venovenous extracorporeal membrane oxygenation (ECMO). Methods: This study was a randomized, double-blind, placebo-controlled phase II pilot trial at two medical intensive care units at the Medical University of Vienna, Austria. Adults with venovenous ECMO were randomly assigned to receive an intravenous infusion of 5 ng/kg/min PGE1 or placebo (0.9% saline) in addition to standard anticoagulation with unfractionated heparin. Measurements and Main Results: The primary outcome was the rate of transfused packed red blood cells per ECMO day. Secondary outcomes were the incidence of and time to clinically overt bleeding and thromboembolic events. A post hoc subgroup analysis included only patients with coronavirus disease (COVID-19). Between September 2016 and April 2021, of 133 screened patients, 50 patients were randomized, of whom 48 received the assigned study medication (24 per group). The transfusion rate was similar between groups (0.41 vs. 0.39; P = 0.733). PGE1 was associated with fewer thromboembolic events (7 vs. 16; P = 0.020) and longer thromboembolism-free time (hazard ratio [HR], 0.302; P = 0.01), fewer clinically overt bleeding events (2 vs. 11; P = 0.017), and longer bleeding-free time (HR, 0.213; P = 0.047). In patients with COVID-19 (n = 25), the HRs for clinically overt bleeding and thromboembolism were 0.276 (95% confidence interval, 0.035-2.186) and 0.521 (95% confidence interval, 0.149-1.825), respectively. Conclusions: Add-on treatment with PGE1 was safe but did not meet the primary endpoint of reducing the rate of red blood cell transfusions in patients receiving venovenous ECMO. Larger studies need to evaluate the safety and efficacy of additional PGE1 in ECMO. Clinical trial registered with EudraCT (2015-005014-30) and www.clinicaltrials.gov (NCT02895373).

Intravascular Versus Surface Cooling in Patients Resuscitated From Cardiac Arrest: A Systematic Review and Network Meta-Analysis With Focus on Temperature Feedback.

OBJECTIVE: The aim of the study was to compare the effect of intravascular cooling (IC), surface cooling with temperature feedback (SCF), and surface cooling without temperature feedback (SCnoF) on neurologic outcome and survival in patients successfully resuscitated from cardiac arrest (CA) and treated with targeted temperature management (TTM) at 32-34°C. DATA SOURCES: We performed a systematic review on Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE, SCOPUS, CINAHL, Web of Science, and Clinical Trials up to June 30, 2021. STUDY SELECTION: We included randomized and nonrandomized studies on IC, SCF, and SCnoF in adult humans resuscitated from CA undergoing TTM, reporting neurologic outcome or survival. DATA EXTRACTION: We performed a network meta-analysis to assess the comparative effects of IC, SCF, and SCnoF. The overall effect between two cooling methods included the effect of direct and indirect comparisons. Results are given as odds ratios (OR) and 95% CIs. Rankograms estimated the probability of TTM methods being ranked first, second, and third best interventions. DATA SYNTHESIS: A total of 14 studies involving 4,062 patients met the inclusion criteria. Four studies were randomized controlled studies, and 10 studies were nonrandomized observational studies. IC compared with SCnoF was significantly associated with better neurologic outcome (OR, 0.6; 95% CI, 0.49-0.74) and survival (OR, 0.8; 95% CI, 0.66-0.96). IC compared with SCF, and SCF compared with SCnoF did not show significant differences in neurologic outcome and survival. The rankogram showed that IC had the highest probability to be the most beneficial cooling method, followed by SCF and SCnoF. CONCLUSIONS: Our results suggest that in patients resuscitated from CA and treated with TTM at 32-34°C, IC has the highest probability of being the most beneficial cooling method for survival and neurologic outcome.

Can simvastatin reduce COPD exacerbations? A randomised double-blind controlled study.

BACKGROUND: Several studies have shown that statins have beneficial effects in COPD regarding lung function decline, rates and severity of exacerbation, hospitalisation and need for mechanical ventilation. METHODS: We performed a randomised double-blind placebo-controlled single-centre trial of simvastatin at a daily dose of 40 mg versus placebo in patients with Global Initiative for Chronic Obstructive Lung Disease criteria grades 2-4 at a tertiary care pulmonology department in Austria. Scheduled treatment duration was 12 months and the main outcome parameter was time to first exacerbation. RESULTS: Overall, 209 patients were enrolled. In the 105 patients taking simvastatin, time to first exacerbation was significantly longer compared to the 104 patients taking placebo: median 341 versus 140 days (log-rank test p<0.001). Hazard ratio for risk of first exacerbation for the simvastatin group was 0.51 (95% CI 0.34-0.75; p=0.001). Rate of exacerbations was significantly lower with simvastatin: 103 (41%) versus 147 (59%) (p=0.003). The annualised exacerbation rate was 1.45 events per patient-year in the simvastatin group and 1.9 events per patient-year in the placebo group (incidence rate ratio 0.77, 95% CI 0.60-0.99). We found no effect on quality of life, lung function, 6-min walk test and high-sensitivity C-reactive protein. More patients dropped out in the simvastatin group compared to the placebo group (39 versus 29). CONCLUSION: In our single-centre RCT, simvastatin at a dose of 40 mg daily significantly prolonged time to first COPD exacerbation and reduced exacerbation rate.

Prevalence and Clinical Impact of Reduced Coagulation Factor XII Activity in Patients Receiving Extracorporeal Membrane Oxygenation.

OBJECTIVES: Extracorporeal membrane oxygenation provides large surface exposure to human blood leading to coagulation activation. Only limited clinical data are available on contact activation and coagulation factor XII activity in extracorporeal membrane oxygenation patients. DESIGN: Prospective cohort study. SETTING: Three medical ICUs at the Medical University of Vienna. PATIENTS: Adult patients receiving venovenous or venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in coagulation factor XII activity in response to extracorporeal membrane oxygenation. Secondary outcomes included the prevalence of reduced coagulation factor XII activity (< 60%) among patients receiving extracorporeal membrane oxygenation and association of coagulation factor XII activity with thromboembolic and bleeding complications. An exploratory endpoint was the association of coagulation factor XII activity and activated partial thromboplastin time in heparinase-treated samples in vitro. Fifty-one patients with a total of 117 samples were included in the study between July 2018 and February 2020. Fifty patients (98%) had reduced coagulation factor XII activity at any timepoint during extracorporeal membrane oxygenation. Median coagulation factor XII activity during extracorporeal membrane oxygenation treatment was 30% (interquartile range, 21.5-41%) and increased after discontinuation (p = 0.047). Patients with thromboembolic complications had higher median coagulation factor XII activity during extracorporeal membrane oxygenation (34% vs 23%; p = 0.023). The odds of a thromboembolic event increased by 200% per tertile of median coagulation factor XII activity (crude odds ratio, 3.034; 95% CI, 1.21-7.63). No association with bleeding was observed. In heparinase-treated samples, coagulation factor XII activity correlated well with activated partial thromboplastin time (r = -0.789; p = 0.007). CONCLUSIONS: We observed a high prevalence of reduced coagulation factor XII activity in adult patients on extracorporeal membrane oxygenation, which may confound activated partial thromboplastin time measurements and limit its clinical usefulness for monitoring and titrating anticoagulation with unfractionated heparin. Lower coagulation factor XII activity was associated with less thromboembolic complications, which may highlight the potential of coagulation factor XII to serve as a target for anticoagulation in extracorporeal membrane oxygenation.

Short- and intermediate-term effects of a hospital-integrated walk-in clinic on emergency department-visits and case mix.

BACKGROUND AND IMPORTANCE: Emergency department (ED) admissions have been rising over the last decades, especially in countries without any effective gate-keeping functions. Integration of walk-in clinics into the hospital might reduce ED-visits. Over a longer period, however, the additional service of a walk-in clinic might attract even more patients, nullifying an initial decrease in patients for the ED. OBJECTIVES, DESIGN, SETTINGS AND PARTICIPANTS: This study aimed to determine short- and intermediate-term changes after the implementation of a hospital-integrated walk-in clinic. This is an observational study using routinely-collected health data. Study setting was the ED of a large tertiary care hospital in Austria, a country with universal health care and no regulations regarding level of care. OUTCOMES MEASURE AND ANALYSIS: ED-visits were compared between before (2015) and after (2017 and 2018) establishment of a hospital-integrated walk-in clinic. MAIN RESULTS: Total ED-visits decreased from 87,624 in 2015 to 67,479 in 2017, and 67,871 in 2018 (p < 0.001), mainly due to a decrease in non-urgent (ESI 4 & 5) cases (45,715 (54.1%) in 2015; 33,142 (51.3%) in 2017; 30,846 (47.5%) in 2018; short term OR non-urgent vs. urgent: 0.89 (95% CI 0.88-0.91); intermediate term OR urgent vs. non-urgent: 0.76 (95% CI 0.78-0.75)). A total of 2611 (13%) (2017) and 1714 (8.5%) (2018) patients were referred back to the ED. CONCLUSIONS: After the introduction of the walk-in clinic, ED-visits declined significantly. This remained stable over a two-year period. Reduction in ED-visits was mainly due to low-acuity patients not requiring admission to the hospital.

Extreme weather conditions as a gender-specific risk factor for acute myocardial infarction.

BACKGROUND: Acute coronary syndrome is a disease with high prevalence and high mortality. Exposure to heat or cold increases the risks of myocardial infarction significantly. Gender-specific effects of this have not yet been examined. Our goal was to determine whether extreme weather conditions, which become more and more frequent, are gender-specific risk factors for myocardial infarction, in order to help provide faster diagnosis and revascularization therapy for patients. METHODS: We analysed the incidence of ST-elevation myocardial infarction (STEMI) in a large urban area over a 65-months period in a cohort study. A day was the unit of analysis. Incidence rate ratios (IRR) with Poisson regression models were calculated. All patients with STEMI on Saturdays and Sundays were included. Gender, high or low perceived temperatures (PT), a function of temperature, wind speed and humidity, and meteorological cold and heat warnings by the Austrian Central Institute for Meteorology and Geodynamics (ZAMG) were considered as risk factors. RESULTS: During the 562 days of the study period, a total of 1109 patients with STEMI (803; 72% men, mean age 61;14 years) were included. The gender difference between men and women was much more pronounced on cold (0 °C) days (85% of patients male; 1.8 per day) than on hot (20 °C) days (71% male; 1.4 per day) or days without extreme temperatures (72% male; 1.4 per day). We found significant interaction between gender and cold days (IRR of the interaction term 2.3 (95% CI 1.2-4.6), p = 0.02). No gender-specific effect was observed on warm days (IRR for interaction 0.9 (95% CI 0.6-1.3), p = 0.3). CONCLUSION: Low perceived temperature pronouncedly increases the already elevated risk for STEMI in males. Whether this effect is based on gender alone, or on one of the cardiovascular risk factors which are more common in men, is up to further study.

Impact of more conservative European Society of Cardiology guidelines on the management of patients with acute chest pain.

OBJECTIVE: Early diagnosis or rule-out of acute coronary syndrome (ACS) is a key competence of emergency medicine. Changes in the NSTE-ACS guidelines of the European Society of Cardiology (ESC) in 2015 and 2020 both warranted a henceforth more conservative approach regarding high-sensitivity troponin t (hsTnt) testing. We aimed to assess the impact of more conservative guidelines on the frequency of early rule-out and prolonged observation with repeated hsTnt testing at a high-volume tertiary care emergency department. PATIENTS AND METHODS: We conducted a pre- and post-changeover analysis 3 months before and 3 months after transition from less (hsTnt cut-off 30 ng/L, 3-hour rule-out) to more conservative (hsTnt cut-off 14 ng/L, 1-hour rule-out) guidelines in 2015, comparing proportions of patients requiring repeated testing. RESULTS: We included 5442 cases of symptoms suspicious of acute cardiac origin (3451 before, 1991 after, 2370 (44%) female, age 55 (SD 19) years). The proportion of patients fulfilling early-rule out criteria decreased from 68% (2348 patients) before to 60% (1195 patients) with the 2015 guidelines (P < .01). Those requiring repeated testing significantly (P < .01) increased from 22% (743 patients) to 25% (494 patients). Positive results in repeated testing significantly (P = .02) decreased from 43% (320 patients) to 37% (181 patients). Invasive diagnostics were performed in 91 patients (2.6%) before and in 75 patients (3.8%) after (P = .02) the guideline revision. CONCLUSION: The implementation of the more conservative 2015 ESC guidelines led to a minor rise in prolonged observations because of an increase in negative repeated testing and to an increase in invasive procedures.

Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy.

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.

Generalisability of randomised trials evaluating perioperative ß-blocker therapy in noncardiac surgery.

BACKGROUND: The limited applicability of evidence from RCTs in real-word practice is considered a potential bottleneck for evidence-based practice but rarely systematically assessed. Using our failure to recruit patients into a perioperative beta-blocker trial, we set out to analyse the restrictiveness and generalisability of trial eligibility criteria in a real-world cohort. METHODS: We prospectively included adult patients (≥18 yr) scheduled for elective noncardiac surgery at an academic tertiary care facility who were screened for inclusion in a planned perioperative beta-blocker RCT, which was terminated owing to recruitment failure. The primary outcome was the proportion of screened patients who matched the eligibility criteria of 36 published RCTs included in a large Cochrane meta-analysis on perioperative beta-blocker therapy. The pragmatic/explanatory level of each RCT was assessed using the PRagmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2) score, which ranges from 9 points (indicating a very explanatory study) to 45 points (indicating a very pragmatic study). RESULTS: A total of 2241 patients (54% female, n=1215; 52 [standard deviation, 20] yr) were included for the assessment of trial eligibility between October 2015 and January 2016. Only a small proportion of patients matched the inclusion and exclusion criteria for each of the 36 RCTs, ranging from 53% to 0%. The average proportion of patients who did match the eligibility criteria of all 36 RCTs was 6.5% (n=145; 95% confidence interval, 6.3-6.6). A higher PRECIS-2 score was associated with a higher proportion of matching patients (P<0.001). CONCLUSIONS: Trial eligibility criteria in perioperative beta-blocker therapy trials are overly restrictive and not generalisable to a real-world surgical population. CLINICAL TRIAL REGISTRATION: EudraCT#: 2015-002366-23.

Impact of Infant Positioning on Cardiopulmonary Resuscitation Performance During Simulated Pediatric Cardiac Arrest: A Randomized Crossover Study.

OBJECTIVES: The primary objective was to determine the impact of infant positioning on cardiopulmonary resuscitation performance during simulated pediatric cardiac arrest. DESIGN: A single-center, prospective, randomized, unblinded manikin study. SETTING: Medical university-affiliated simulation facility. SUBJECTS: Fifty-two first-line professional rescuers (n = 52). INTERVENTIONS: Performance of cardiopulmonary resuscitation was determined using an infant manikin model in three different positions (on a table [T], on the provider's forearm with the manikin's head close to the provider's elbow [P], and on the provider's forearm with the manikin's head close to the provider's palm [D]). For the measurement of important cardiopulmonary resuscitation performance variables, a commercially available infant simulator was modified. In a randomized sequence, healthcare professionals performed single-rescuer cardiopulmonary resuscitation for 3 minutes in each position. Performances of chest compression (primary outcome), ventilation, and hands-off time were analyzed using a multilevel regression model. MEASUREMENTS AND MAIN RESULTS: Mean (± SD) compression depth significantly differed between table and the other two manikin positions (31 ± 2 [T], 29 ± 3 [P], and 29 ± 3 mm [D]; overall p < 0.001; repeated measures design adjusted difference: T vs P, -2 mm [95% CI, -2 to -1 mm]; T vs D, -1 mm [95% CI, -2 to -1 mm]). Secondary outcome variables showed no significant differences. CONCLUSIONS: Compressions were significantly deeper in the table group compared to positions on the forearm during cardiopulmonary resuscitation, yet the differences were small and perhaps not clinically important.

Exclusion of pregnancy in dialysis patients: diagnostic performance of human chorionic gonadotropin.

BACKGROUND: A positive pregnancy test in acute or chronically ill patients has implications for the use of potentially mutagenic or teratogenic products in urgent medical therapies such as the use of chemotherapies or therapies with immunosuppressants, for anesthesia, and for time-sensitive indications like urgent surgery or organ Transplantation. Despite a lack of evidence, it is currently believed that human chorionic gonadotropin serum concentrations are always elevated in female dialysis patients even without pregnancy. It is also believed that human chorionic gonadotropin cannot be used to confirm or exclude pregnancy. METHODS: Human chorionic gonadotropin was examined in female dialysis patients (18-50 years of age), and was classified as positive above 5 mlU/ml. In addition, fertility status was determined. For an enhanced index test, the cut-off of 5 mIU/ml was used for potentially fertile patients and 14 mIU/ml for infertile patients to calculate diagnostic test accuracy. The ideal cut-off for human chorionic gonadotropin was estimated using Liu's method with bootstrapped 95% confidence intervals. Predictors of human chorionic gonadotropin increase were analyzed using multivariable linear regression. RESULTS: Among 71 women, two (2.8%) were pregnant, 46 (64.8%) potentially fertile, and 23 (32.4%) infertile. We observed human chorionic gonadotropin concentrations > 5 mIU/ml in 10 patients, which had a sensitivity of 100% (95% confidence interval: 100 to 100), a specificity of 86% (95% confidence interval: 77 to 94), a positive predictive value of 17% (95% confidence interval: 8 to 25) and a negative predictive value of 100% (95% confidence interval: 100 to 100) for the diagnosis of pregnancy. Using a cut-off > 14 mIU/ml for infertile patients or the exclusion of infertile patients increased specificity to 93% or 98%, respectively. The ideal cut-off was 25 mIU/ml (95% confidence interval: 17 to 33). Pregnancy and potential fertility, but not age, were independent predictors of human chorionic gonadotropin. CONCLUSION: Human chorionic gonadotropin is elevated > 5mIU/ml in 14.5% of non-pregnant dialysis patients of child-bearing age. In potentially fertile women, this cut-off can be used to exclude pregnancy. In case of an unknown fertility status, the ideal human chorionic gonadotropin cut-off was 25 mIU/ml.

Early identification of patients with chest pain at very low risk of acute myocardial infarction using clinical information and ECG only.

BACKGROUND: A considerable proportion of patients with angina-like symptoms in an emergency department have very low pretest probability for acute myocardial infarction (AMI). Numerous algorithms exist for the exclusion of AMI, usually including laboratory tests. We aimed to investigate whether patients with very low risk can safely be identified by ECG and clinical information without biomarker testing, contributing to saving time and costs. METHODS: Prospective diagnostic test accuracy study. We included all consecutive patients presenting with angina at the department of emergency medicine of a tertiary care hospital during a 1-year period. Using clinical information without biomarker testing and ECG, the "Mini-GRACE score," based on the well-established GRACE-score without using laboratory parameters was calculated. In a cohort design we compared the index test Mini-GRACE to AMI as reference standard in the final diagnosis using standard measures of diagnostic test accuracy. RESULTS: We included 2755 patients (44% female, age 44 ± 17 years). AMI was diagnosed in 103 (4%) patients, among those 44% with STEMI. Overall 2562 patients (93%) had a negative "Mini-GRACE," four (0.2%) of these patients had myocardial infarction, and this results in a sensitivity of 96.1% (95% CI 90.4%-98.9%), specificity 96.5% (95.7%-97.1%), positive predictive value 51.3% (46.3%-56.3%) and negative predictive value 99.8% (99.6%-99.9%). Model performance according to C statistic (0.90) and Brier score (0.0045) was excellent. In rule-out patients 30-day mortality was 0.3% and 1-year mortality was 0.8%. CONCLUSIONS: Patients with very low risk of AMI can be identified with high certainty using clinical information without biomarker testing and ECG. Cardiac biomarkers might be avoided in such cases, potentially leading to a significant cost reduction.

Risk stratification in acute coronary syndrome: Evaluation of the GRACE and CRUSADE scores in the setting of a tertiary care centre.

OBJECTIVE: Risk assessment plays a decisive role in the management of acute coronary syndrome (ACS). The GRACE and the CRUSADE scores are among the most frequently used risk assessment tools. We aimed to compare the performance of the GRACE and CRUSADE risk scores to predict in-hospital mortality and major bleeding in a contemporary ACS population at a high-volume academic hospital. METHODS: All patients treated for ACS from January 1, 2006 to December 31, 2015 at a tertiary care centre were prospectively enrolled. We calculated GRACE and CRUSADE risk scores. We compared the discrimination capacity of both scores for in-hospital mortality and major bleeding. RESULTS: In total 4087 patients (1151 [28.2%] female; age 62 ± 14 years) were included. Among these 2218 (54.3%) were diagnosed with ST-elevation myocardial infarction, 113 (2.8%) died in hospital and major bleeding occurred in 65 (1.6%). Discrimination capacity for in-hospital mortality of the GRACE score was superior to the CRUSADE score (receiver operator characteristic area under the curve (AUC) 0.91 (95% CI 0.89-0.93) vs 0.83 (95% CI 0.80-0.86); P < .01). Performance for major bleeding differed but was poor for both scores (AUC 0.71 [0.65-0.76] for GRACE vs 0.61 [0.55-0.68] for CRUSADE; P < .01). CONCLUSION: The GRACE score appears to be superior over CRUSADE to predict in-hospital mortality. Major bleeding is rare in the era of primary PCI and performance of both scores for this outcome was poor.

Torque Teno Virus for Risk Stratification of Acute Biopsy-Proven Alloreactivity in Kidney Transplant Recipients.

BACKGROUND: Drug-induced immunosuppression in kidney transplant recipients is crucial to prevent allograft rejection, but increases risk for infectious disease. Immunologic monitoring to tailor immunosuppressive drugs might prevent alloreactivity and adverse effects simultaneously. The apathogenic torque teno virus (TTV) reflects the immunocompetence of its host and might act as a potential candidate for a holistic monitoring. METHODS: We screened all 1010 consecutive patients from the prospective Vienna Kidney Transplant Cohort Study for availability of allograft biopsies and adequately stored sera for TTV quantification by polymerase chain reaction. RESULTS: Patients with acute biopsy-proven alloreactivity according to the Banff classification (n = 33) showed lower levels of TTV in the peripheral blood compared to patients without rejection (n = 80) at a median of 43 days before the biopsy. The risk for alloreactivity decreased by 10% per log level of TTV copies/mL (risk ratio, .90 [95% confidence interval, .84-.97]; P = .005). TTV levels >1 × 106 copies/mL exclude rejection with a sensitivity of 94%. Multivariable generalized linear modeling suggests an independent association between TTV level and alloreactivity. CONCLUSIONS: TTV is a prospective biomarker for risk stratification of acute biopsy-proven alloreactivity in kidney transplant recipients and might be a potential tool to tailor immunosuppressive drug therapy.

Major Adverse Cardiac Events and Mortality Associated with Electroconvulsive Therapy: A Systematic Review and Meta-analysis.

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.

An integrative approach for the assessment of peritubular capillaritis extent and score in low-grade microvascular inflammation-associations with transplant glomerulopathy and graft loss.

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.

Quantification of Torque Teno Virus Viremia as a Prospective Biomarker for Infectious Disease in Kidney Allograft Recipients.

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.