Search

Computer-assisted reporting (CAR) tools were suggested to improve radiology report quality by context-sensitively recommending key imaging biomarkers. However, studies evaluating machine learning (ML) algorithms on cross-lingual ontological (RadLex) mappings for developing embedded CAR algorithms are lacking. Therefore, we compared ML algorithms developed on human expert-annotated features against those developed on fully automated cross-lingual (German to English) RadLex mappings using 206 CT reports of suspected stroke. Target label was whether the Alberta Stroke Programme Early CT Score (ASPECTS) should have been provided (yes/no:154/52). We focused on probabilistic outputs of ML-algorithms including tree-based methods, elastic net, support vector machines (SVMs) and fastText (linear classifier), which were evaluated in the same 5 × fivefold nested cross-validation framework. This allowed for model stacking and classifier rankings. Performance was evaluated using calibration metrics (AUC, brier score, log loss) and -plots. Contextual ML-based assistance recommending ASPECTS was feasible. SVMs showed the highest accuracies both on human-extracted- (87%) and RadLex features (findings:82.5%; impressions:85.4%). FastText achieved the highest accuracy (89.3%) and AUC (92%) on impressions. Boosted trees fitted on findings had the best calibration profile. Our approach provides guidance for choosing ML classifiers for CAR tools in fully automated and language-agnostic fashion using bag-of-RadLex terms on limited expert-labelled training data.

Purpose: To assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x‑rays for early breast cancer., Methods: We prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x‑rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated., Results: There were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N‑terminal fragment of B‑type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279)., Conclusion: Troponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.

As stated by the Fleischner Society, an additional computed tomography (CT) scan in expiration is beneficial in patients with chronic obstructive pulmonary disease (COPD). It was thus the aim of this study to evaluate the radiation risk of a state-of-the-art paired inspiratory-expiratory chest scan compared to inspiration-only examinations. Radiation doses to 28 organs were determined for 824 COPD patients undergoing routine chest examinations at three different CT systems-a conventional multi-slice CT (MSCT), a 2nd generation (2nd-DSCT), and 3rd generation dual-source CT (3rd-DSCT). Patients examined at the 3rd-DSCT received a paired inspiratory-expiratory scan. Organ doses, effective doses, and lifetime attributable cancer risks (LAR) were calculated. All organ and effective doses were significantly lower for the paired inspiratory-expiratory protocol (effective doses: 4.3 ± 1.5 mSv (MSCT), 3.0 ± 1.2 mSv (2nd-DSCT), and 2.0 ± 0.8 mSv (3rd-DSCT)). Accordingly, LAR was lowest for the paired protocol with an estimate of 0.025 % and 0.013% for female and male patients (50 years) respectively. Image quality was not compromised. Paired inspiratory-expiratory scans can be acquired on 3rd-DSCT systems at substantially lower dose and risk levels when compared to inspiration-only scans at conventional CT systems, offering promising prospects for improved COPD diagnosis.

Purpose: Quantified computed tomography (qCT) is known for correlations with airflow obstruction and fibrotic changes of the lung. However, as qCT studies often focus on diseased and elderly subjects, current literature lacks physiological qCT values during body development. We evaluated chest CT examinations of a healthy cohort, reaching from infancy to adulthood, to determine physiological qCT values and changes during body development., Method: Dose-optimized chest CT examinations performed over the last 3 years using a dual-source CT were retrospectively analysed. Exclusion criteria were age >30 years and any known or newly diagnosed lung pathology. Lung volume, mean lung density, full-width-at-half-maximum and low attenuated volume (LAV) were semi-automated quantified in 151 patients. qCT values between different age groups as well as unenhanced (Group 1) and contrast-enhanced (Group 2) protocols were compared. Models for projection of age-dependant changes in qCT values were fitted., Results: Significant differences in qCT parameters were found between the age groups from 0 to 15 years (p < 0.05). All parameters except LAV merge into a plateau level above this age as shown by polynomial models (r2 between 0.85 and 0.67). In group 2, this plateau phase is shifted back around five years. Except for the volume, significant differences in all qCT values were found between group 1 and 2 (p < 0.01)., Conclusion: qCT parameters underly a specific age-dependant dynamic. Except for LAV, qCT parameters reach a plateau around adolescence. Contrast-enhanced protocols seem to shift this plateau backwards., Competing Interests: The authors have declared that no competing interests exist.

Ventilation heterogeneity is frequent in bronchial asthma and can be assessed using multiple breath wash-out testing (MBW). Most data is available in paediatric patients and using nitrogen as a tracer gas. We aimed to evaluate sulphur hexafluoride (SF 6 ) MBW in adult asthmatics. Spirometry, whole-body plethysmography, impulse oscillometry and SF 6 -MBW were prospectively performed. MBW parameters reflecting global (lung clearance index, LCI), acinar (S acin ) and conductive (S cond ) ventilation heterogeneity were derived from three consecutive wash-outs. LCI was calculated for the traditional 2.5% and an earlier 5% stopping point that has the potential to reduce wash-out times. 91 asthmatics (66%) and 47 non-asthmatic controls (34%) were included in final analysis. LCI 2.5 and LCI 5 were higher in asthmatics (p < 0.001). Likewise, S acin and S cond were elevated (p < 0.001 and p < 0.01). Coefficient of variation was 3.4% for LCI 2.5 and 3.5% for LCI 5 in asthmatics. Forty-one asthmatic patients had normal spirometry. ROC analysis revealed an AUC of 0.906 for the differentiation from non-asthmatic controls exceeding diagnostic performance of individual and conventional parameters (AUC = 0.819, p < 0.05). SF 6 -MBW is feasible and reproducible in adult asthmatics. Ventilation heterogeneity is increased as compared to non-asthmatic controls persisting in asthmatic patients with normal spirometry. Diagnostic performance is not affected using an earlier LCI stopping point while reducing wash-out duration considerably.

In postural stress, an increased preload volume leads to higher stroke volume (SV) according to the Frank-Starling law of the heart. The present study aimed to evaluate the hemodynamic response to postural stress using non-invasive inert gas rebreathing (IGR) in patients with normal as well as impaired left ventricular function. Hemodynamic measurements were performed in 91 patients undergoing cardiac magnetic resonance imaging (CMR). Mean cardiac output and SV determined by IGR were 4.4±1.3 l/min and 60±19 ml in the upright position, which increased significantly to 5.0±1.2 l/min and 75±23 ml in the supine position (P<0.01). Left ventricular systolic function was normal [ejection fraction (EF) ≥55%] in 42 patients as determined by CMR. In 21 patients, EF was mildly abnormal (45-54%), in 16 patients moderately abnormal (30-44%) and in 12 patients severely abnormal (<30%). An overall trend for a lower percentage change in SV (%ΔSV) was indicated with increasing impairment of ejection fraction. In patients with abnormal EF in comparison to those with normal EF, the %ΔSV was significantly lower (13% vs. 22%; P=0.03). Non-invasive measurement of cardiac function using IGR during postural changes may be feasible and detected significant difference in %ΔSV in patients with normal and impaired EF according to the Frank-Starling law of the heart. Several clinical scenarios including cases of heart rhythm disturbances or pulmonary or congenital heart disease are worthy of further investigation.

Introduction: Quantitative computed tomography (qCT) is an emergent technique for diagnostics and research in patients with chronic obstructive pulmonary disease (COPD). qCT parameters demonstrate a correlation with pulmonary function tests and symptoms. However, qCT only provides anatomical, not functional, information. We evaluated five distinct, partial-machine learning-based mathematical models to predict lung function parameters from qCT values in comparison with pulmonary function tests., Methods: 75 patients with diagnosed COPD underwent body plethysmography and a dose-optimized qCT examination on a third-generation, dual-source CT with inspiration and expiration. Delta values (inspiration-expiration) were calculated afterwards. Four parameters were quantified: mean lung density, lung volume low-attenuated volume, and full width at half maximum. Five models were evaluated for best prediction: average prediction, median prediction, k -nearest neighbours (kNN), gradient boosting, and multilayer perceptron., Results: The lowest mean relative error (MRE) was calculated for the kNN model with 16%. Similar low MREs were found for polynomial regression as well as gradient boosting-based prediction. Other models led to higher MREs and thereby worse predictive performance. Beyond the sole MRE, distinct differences in prediction performance, dependent on the initial dataset (expiration, inspiration, delta), were found., Conclusion: Different, partially machine learning-based models allow the prediction of lung function values from static qCT parameters within a reasonable margin of error. Therefore, qCT parameters may contain more information than we currently utilize and can potentially augment standard functional lung testing.

In patients with chronic obstructive pulmonary disease (COPD), cardiovascular comorbidities are highly prevalent and associated with considerable morbidity and mortality. This coincidence is increasingly seen in context of a "cardiopulmonary continuum" rather than being simply attributed to shared risk factors such as cigarette smoking. Overlapping symptoms such as dyspnea or chest pain lead to a worse prognosis due to missed concomitant diagnoses. Moreover, medication is often withheld as a result of unfounded concerns about side effects. Despite the frequent coincidence, current guidelines are still mostly restricted to the management of the individual disease. Future diagnostic and therapeutic strategies should therefore be guided by an integrative perspective as well as a refined phenotyping of disease entities.

Purpose: Dronedarone is a multichannel-blocking antiarrhythmic drug for the treatment of atrial fibrillation. Observational data hypothesized a cardioprotective effect. In an in vitro endothelial cell-platelet model, we evaluated the molecular atheroprotective effects of dronedarone., Methods: Following a 24-h incubation of human umbilical vein endothelial cells (HUVECs) with dronedarone (concentration 50, 100, and 150 ng/mL), they were then stimulated for 1 h with lipopolysaccharide (LPS) and were subsequently incubated in direct contact with thrombin-activated platelets. After incubation, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, urokinase-type plasminogen activator receptor (uPAR), and membrane type 1 matrix metalloproteinase (MT1-MMP) on endothelial cells were measured by flow cytometry., Results: Preincubation with 150 ng/mL of dronedarone reduced the expression of uPAR on endothelial cells after proinflammatory stimulation with LPS and also by direct endothelial contact with activated platelets (p = 0.0038). In contrast, the expression of CD40L and CD62P on platelets after proinflammatory stimulation with thrombin was significantly increased through direct preincubation with 50/100/150 ng/mL of dronedarone. However, dronedarone had no effects on the expression of MT1-MMP and ICAM-1 in HUVECs., Conclusion: In this in vitro analysis, dronedarone directly increased platelet activation but showed significant direct effects on endothelial cells and indirect effects on platelets on selected markers of atherosclerosis., (© 2019 S. Karger AG, Basel.)

Airways obstruction is frequent in patients with pulmonary hypertension (PH). Small airway disease (SAD) was identified as a major contributor to resistance and symptoms. However, it is easily missed using current diagnostic approaches. We aimed to evaluate more elaborate diagnostic tests such as impulse oscillometry (IOS) and SF₆-multiple-breath-washout (MBW) for the assessment of SAD in PH. Twenty-five PH patients undergoing body-plethysmography, IOS and MBW testing were prospectively included and equally matched to pulmonary healthy and non-healthy controls. Lung clearance index (LCI) and acinar ventilation heterogeneity (S acin ) differed significantly between PH, healthy and non-healthy controls. Likewise, differences were found for all IOS parameters between PH and healthy, but not non-healthy controls. Transfer factor corrected for ventilated alveolar volume (TLCO/VA), frequency dependency of resistance (D5-20), resonance frequency (F res ) and S acin allowed complete differentiation between PH and healthy controls (AUC (area under the curve) = 1.0). Likewise, PH patients were separated from non-healthy controls (AUC 0.762) by D5-20, LCI and conductive ventilation heterogeneity (S cond ). Maximal expiratory flow (MEF) values were not associated with additional diagnostic values. MBW and IOS are feasible in PH patients both providing additional information. This can be used to discriminate PH from healthy and non-healthy controls. Therefore, further research targeting SAD in PH and evaluation of therapeutic implications is justified.

Purpose: The importance of spirometry for management of COPD was reduced in the 2017 revision of the GOLD report. CT derived airway measurements show strong correlations with lung function tests and symptoms. However, these correlations are specific to the airway localization, and currently there is no evidence for the ideal spot. Therefore, the aim of this prospective study was to systematically correlate CT derived airway measurements with extensive lung function testing., Methods and Materials: 65 patients with diagnosed COPD underwent body plethysmography, impulse oscillometry and dose optimized qCT examination (Somatom Force, Healthineers, Germany) in inspiration and expiration. Eight airway parameters (e.g. outer diameter, maximal wall thickness) were acquired for both scans in every lobe for the third to fifth generation bronchus and correlated with the lung function tests., Results: The most significant correlations between airway parameters were found for the third generation bronchus of the upper left lobe during expiration (25 out of 48 correlation pairs, mean r = -0.39) and for the third generation bronchus of the upper right lobe during inspiration (9 out of 48 correlation pairs, mean r = -0.25). No significant correlations were for example found for the upper right lobe in expiration., Conclusion: Correlations between airway parameters and lung function tests vary widely between lobes, bronchus generations and breathing states. Our work suggests that the third generation bronchus of the upper left lobe in expiration could be the preferred localization for airway quantification in future studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Diagnostic guidelines for chronic obstructive pulmonary disease (COPD) are based on spirometry and clinical criteria. However, this does not address the pathophysiological complexity of the disease sufficiently. Until now, inspiratory chest computed tomography (CT) has been considered as the preferred imaging method in these patients. We hypothesized that expiratory CT may be superior to demonstrate pathophysiological changes. The aim of this prospective study was to systematically compare lung function tests with quantified CT parameters in inspiration and expiration., Materials and Methods: Forty-six patients with diagnosed COPD underwent spirometry, body plethysmography, and dose-optimized CT in maximal inspiration and expiration. Four quantified CT parameters were acquired in inspiration, expiration, and their calculated delta values. These parameters were correlated with seven established lung function parameters., Results: For inspiratory scans, a weak-to-moderate correlation with the lung function parameters was found. These correlations significantly improved when adding the expiratory scan ( p < 0.05). Moreover, some parameters showed a significant correlation only in expiratory datasets. Calculated delta values showed even stronger correlation with lung function testing., Conclusions: Expiratory quantified CT and calculated delta values significantly improve the correlation with lung function parameters. Thus, an additional expiratory CT may improve image-based phenotyping of patients with COPD.

The human arterial vascular tree can be described by multicompartment models using electrical components. First introduced in the 1960s by Noordergraaf and Westerhof, these hardware-based approaches required several simplifications. We were able to remove the restrictions using modern software simulation tools and improve overall model quality considerably. Whereas the original Westerhof model consisted of 121 Windkessel elements, the refined model has 711 elements and gives realistic pulse waveforms of the aorta and brachial and radial arteries with realistic blood pressures. Moreover, novel insights concerning the formation of the physiological aortic-to-radial transfer function were gained. Its being potentially due to the coupling of many small resonant elements gives new impetus to the discussion of arterial pressure wave reflection. The individualized transfer function derived from our improved model incorporates distinct patient characteristics and can potentially be used for estimation of central blood pressure values. NEW & NOTEWORTHY We were able to find an individualized transfer function giving realistic pulse waveforms and blood pressures using a multicompartment model of the arterial system. Based on the hardware-built Westerhof approach, several simplifications initially introduced in the 1960s could be reversed using software simulation. Overall model quality was improved considerably, and multiple coupled resonances were identified as potential explanation for the formation of the aortic-to-radial transfer function, giving new impetus to the discussion of arterial pressure wave reflection.

Background: Multiple breath washout (MBW) became a valuable research tool assessing ventilation heterogeneity. However, routine clinical application still faces several challenges. Deriving MBW parameters from three technically acceptable measurements according to current recommendations prolongs test times. We therefore aimed to evaluate reporting only duplicate measurements in healthy adults and pulmonary disease., Methods: One hundred and fifty-three subjects prospectively underwent conventional lung function testing and closed-circuit SF 6 -MBW. Three technically acceptable MBW-measurements were obtained in 103 subjects., Results: Lung clearance index (LCI) differed significantly among 19 controls (7.4 ± 0.8), 19 patients with sarcoidosis (8.1 ± 1.2), 32 with bronchial asthma (9.2 ± 1.9) and 33 with COPD (10.8 ± 2.2, p < 0.001). Within-test repeatability was high (coefficient of variation between 2.5% in controls and 3.6% in COPD) and remained unchanged when only including the first two measurements. Likewise, LCI remained stable with mean absolute changes ranging from 0.9 ± 0.8% in controls to 1.5 ± 0.9% in COPD (p = 0.1). Mean test time reduction differed significantly between groups reaching 200 s in COPD (p = 0.01)., Conclusions: Duplicate SF 6 -MBW-measurements are sufficient in adult patients with pulmonary disease and healthy controls. LCI values and intra-test repeatability are not affected reducing total test time statistically significant. Our findings have the potential to further facilitate application of MBW in research and clinical routine., Trial Registration: NCT03176745 , June 2, 2017 retrospectively registered.

Purpose: Lipid lowering therapy constitutes the basis of cardiovascular disease therapy. The purpose of this study was to investigate effects of ezetimibe, a selective inhibitor of intestinal cholesterol absorption, on platelets and endothelial cells in an in vitro endothelial cell model., Methods: After a 24h incubation period with ezetimibe (concentrations 1, 50, 100 and 1000ng/ml), human umbilical vein endothelial cells (HUVEC) were stimulated for 1h with lipopolysaccharide (LPS) and were then incubated in direct contact with activated platelets. Following this, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, uPAR, and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analysed by enzyme linked immunosorbent assay for soluble MCP-1, IL-6 and MMP-1., Results: The increased expression of uPAR on endothelial cells by proinflammatory stimulation with LPS and by direct endothelial contact with activated platelets was significantly reduced through pre-incubation with 100ng/ml and 1000ng/ml ezetimibe (p<0.05). Platelets directly incubated with ezetimibe but without endothelial cell contact showed significantly reduced CD62P and CD40L surface expression (p<0.05). Ezetimibe had no significant effects on HUVEC expression of MT1-MMP, ICAM-1 and VCAM-1 and on CD40L expression on platelets in direct contact with endothelial cells. Levels of soluble IL-6 in HUVEC supernatants were significantly lower after pre-incubation with ezetimibe., Conclusion: In this in vitro analysis, ezetimibe directly attenuates platelet activation and has significant endothelial cell mediated effects on selected markers of atherosclerosis., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Electrical velocimetry (EV) is one of the most recent adaptions of impedance cardiography. Previous studies yielded diverging results identifying several factors negatively influencing accuracy. Although electrode arrangement is suspected to be an influencing factor for impedance cardiography in general, no data for EV is available. We aimed to prospectively assess the influence of electrode position on the accuracy and reproducibility of cardiac output (CO) measurements obtained by EV. Two pairs of standard electrocardiographic electrodes were placed at predefined positions of the thorax in 81 patients. The inter-electrode gap was varied between either 5 or 15 cm by caudal movement of the lowest electrode. Measurements were averaged over 20 s and performed twice at each electrode position. Reference values were determined using cardiac magnetic resonance imaging (CMR). Mean bias was 1.2  ±  1.6 l min(-1) (percentage error 22  ±  28%) between COCMR and COEV at the 5 cm gap significantly improving to 0.5  ±  1.6 l min(-1) (8  ±  28%) when increasing the gap (p  <  0.0001). The mean difference between repeated measurements was 0.0  ±  0.3 l min(-1) for the 5 cm and 0.1  ±  0.3 l min(-1) for the 15 cm gap, respectively (p  =  0.3). The accuracy of EV can be significantly improved when increasing the lower inter-electrode gap still exceeding the Critchley and Critchley recommendations. Therefore, absolute values should not be used interchangeably in clinical routine. As the reproducibility was not negatively affected, serial hemodynamic measurements can be reliably acquired in stable patients when the electrode position remains unchanged.

A novel algorithm of impedance cardiography referred to as electrical velocimetry (EV) has been introduced for non-invasive determination of cardiac output (CO). Previous validation studies yielded diverging results and no comparison with the non-invasive gold standard cardiac magnetic resonance imaging (CMR) has been performed. We therefore aimed to prospectively assess the accuracy and reproducibility of EV compared to CMR. 152 consecutive stable patients undergoing CMR were enrolled. EV measurements were taken twice before or after CMR in supine position and averaged over 20 s (AESCULON(®), Osypka Medical, Berlin, Germany). Bland-Altman analysis showed insufficient agreement of EV and CMR with a mean bias of 1.2 ± 1.4 l/min (bias 23 ± 26 %, percentage error 51 %). Reproducibility was high with 0.0 ± 0.3 l/min (bias 0 ± 8 %, percentage error 15 %). Outlier analysis revealed gender, height, CO and stroke volume (SV) by CMR as independent predictors for larger variation. Stratification of COCMR in quintiles demonstrated a good agreement for low values (<4.4 l/min) with bias increasing significantly with quintile as high as 3.1 ± 1.1 l/min (p < 0.001). Reproducibility was not affected (p = 0.71). Subgroup analysis in patients with arrhythmias (p = 0.19), changes in thoracic fluid content (p = 0.51) or left heart failure (p = 0.47) could not detect significant differences in accuracy. EV showed insufficient agreement with CMR and good reproducibility. Gender, height and increasing CO and SV were associated with increased bias while not affecting reproducibility. Therefore, absolute values should not be used interchangeably in clinical routine. EV yet may find its place for clinical application with further investigation on its trending ability pending.

Introduction: The aim of this study was to evaluate the diagnostic and prognostic value of presepsin in patients with severe sepsis and septic shock during the first week of ICU treatment., Methods: In total, 116 patients with suspected severe sepsis or septic shock were included during the first 24 hours of ICU treatment. Blood samples for biomarker measurements of presepsin, procalcitonin (PCT), interleukin 6 (IL-6), C reactive protein (CRP) and white blood cells (WBC) were drawn at days 1, 3 and 8. All patients were followed up for six months. Biomarkers were tested for diagnosis of sepsis, severe sepsis, septic shock and for prognosis of 30-days and 6-months all-cause mortality at days 1, 3 and 8. Diagnostic and prognostic utilities were tested by determining diagnostic cutoff levels, goodness criteria, C-statistics and multivariable Cox regression models., Results: Presepsin increased significantly from the lowest to most severe sepsis groups at days 1, 3 and 8 (test for linear trend P <0.03). Presepsin levels revealed valuable diagnostic capacity to diagnose severe sepsis and septic shock at days 1, 3 and 8 (range of diagnostic area under the curves (AUC) 0.72 to 0.84, P = 0.0001) compared to IL-6, PCT, CRP and WBC. Goodness criteria for diagnosis of sepsis severity were analyzed (≥sepsis, cutoff = 530 pg/ml; ≥severe sepsis, cutoff = 600 pg/ml; ≥septic shock, cutoff = 700 pg/ml; P <0.03). Presepsin levels revealed significant prognostic value for 30 days and 6 months all-cause mortality (presepsin: range of AUC 0.64 to 0.71, P <0.02). Patients with presepsin levels of the 4th quartile were 5 to 7 times more likely to die after six months than patients with lower levels. The prognostic value for all-cause mortality of presepsin was comparable to that of IL-6 and better than that of PCT, CRP or WBC., Conclusions: In patients with suspected severe sepsis and septic shock, presepsin reveals valuable diagnostic capacity to differentiate sepsis severity compared to PCT, IL-6, CRP, WBC. Additionally, presepsin and IL-6 reveal prognostic value with respect to 30 days and 6 months all-cause mortality throughout the first week of ICU treatment., Trial Registration: ClinicalTrials.gov http://NCT01535534. Registered 14 February 2012.

Purpose: Non-invasive inert gas rebreathing (IGR) has shown promising results in the determination of pulmonary blood flow. The volume of the rebreathing bag (V bag) is proposed by the system. However, elderly patients or those with severe pulmonary disease may be unable to rebreathe this volume entirely. We evaluated the effect of adapting V bag on the reproducibility of IGR., Methods: A total of 270 valid measurements were obtained from 45 patients with obstruction (group A), restriction (group B), and in healthy controls (group C). Two measurements for each of three different V bag of 1,200, 1,700, and 2,200 ml were conducted in the supine position., Results: We found no statistically significant difference of the repeated measurements neither between the different V bag in groups A to C nor between the three groups for identical V bag. There was a weak yet significantly worse coefficient of variation between a V bag of 2,200 ml in group A compared with group C with 2,200 and 1,200 ml, respectively. Intraclass correlation coefficient and repeatability coefficient yielded significantly worse values in group A for a V bag of 2,200 ml compared with healthy controls and lower bag volumes. No difference could be found intraclass nor interclass in groups B and C., Conclusions: V bag can be altered between 1,200 and 2,200 ml in most situations without affecting the reproducibility. Attention has to be paid to extreme volumes in obstructive patients. Nevertheless, V bag should be chosen as large as possible and therefore has to be carefully adapted, particularly in patients with obstruction or restriction.

Objectives: A growing interest in monitoring cardiac output (CO) noninvasively has emerged; however, its determination has been difficult using the standard approaches. The aim of this study was to evaluate the accuracy and precision of pulse contour analysis (PCA) compared with cardiac magnetic resonance imaging (CMR)., Design: A single-center prospective study., Setting: A university hospital., Participants: Thirty-nine consecutive stable patients undergoing CMR., Interventions: CO was determined twice by PCA using the Nexfin monitoring system (BMEYE BV, Amsterdam, The Netherlands). Measurements were performed after 10 minutes of rest in a stable supine position immediately before or after the CMR examination., Measurements and Main Results: There was a mean bias of 0.2 ± 1.9 L/min between CMR and PCA and a reproducibility of 0.2 ± 0.6 L/min for PCA. Between 4.8 and 6.3 L/min (second quartile of COCMR), there was a good agreement (mean bias = -0.2 ± 1.3 L/min). Comparing quartile 1 (-1.3 ± 2.0 L/min) overestimating and quartiles 3 (1.4 ± 0.9 L/min) and 4 (0.9 ± 2.0 L/min) underestimating CO, a statistically significant difference was found. The reproducibility was not affected by the quartile (p = 0.23, analysis of variance), whereas there was a significant difference between the nonoutlier and outlier group when using the Mann-Whitney U test (p = 0.02)., Conclusions: Noninvasive PCA allows the safe and economic measurement of CO, yet it still has major limitations. Although the agreement with CMR was acceptable, there was a clinically unacceptable variation; absolute values should not be used interchangeably. These results suggest that therapeutic interventions and clinical decisions should not be based on noninvasive PCA measurements at the present time., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Doppler echocardiography is the method of choice for diagnosis and evaluation of aortic stenosis. However, there are well-known limitations to this method in difficult-to-image patients. Flow acceleration in the left ventricular outflow tract (LVOT) can lead to overestimation of stroke volume (SV) and poor acoustic windows may impede the exact measurement of the LVOT. The present study aimed to evaluate the use of inert gas rebreathing (IGR)-derived SV in this situation., Patients and Methods: We replaced Doppler-derived SV measurements in the continuity equation (method A) by SV determined by IGR (method B) and by thermodilution during right heart catheterization (method C) to calculate the aortic valve area (AVA) in 21 consecutive patients with moderate or severe aortic stenosis., Results: Mean SV and AVA did not differ between methods at 72±21 ml and 0.71±0.2 cm(2) (method A) vs. 66±18 ml and 0.67±0.21 cm(2) (method B) vs. 64±15 ml and 0.67±0.21 cm(2) (method C), respectively (all p-values >0.05). The mean difference and limits of agreement for AVA were 0.04±0.23 cm(2) and -0.40 to 0.47 cm(2) between methods A and B, 0.05±0.14 cm(2) and -0.26 to 0.27 cm(2) between A and C, and -0.05±0.23 cm(2) and -0.45 to 0.35 cm(2) between B and C, respectively (all p-values >0.05)., Conclusion: The presented approach is a reliable method for the calculation of AVA and can add a diagnostic option for the use in difficult-to-image patients. Whereas the use of thermodilution is limited due to its invasive nature, IGR allows the fast and non-invasive determination of cardiac function at low cost.

Background: When assessing the function of the cardiovascular system, cardiac output (CO) is a substantial parameter. For its determination, numerous non-invasive techniques have been proposed in the recent years including inert gas rebreathing (IGR) and impedance cardiography (ICG). The aim of our study was to evaluate whether a novel ICG algorithm (electrical velocimetry) and IGR can be used interchangeably in the clinical setting., Methods: A total of 120 consecutive stable patients were included resulting in two pairs of repeated non-invasive cardiac output measurements., Results: The mean CO was 5.0 ± 1.2 l/min (range 2.6-8.6 l/min) using IGR and 4.4 ± 1.1 l/min (1.7-7.4 l/min) using ICG, respectively. Bland-Altman analysis revealed an acceptable agreement with a mean bias of 0.6 ± 1.2 l/min. We found a high reproducibility with a mean bias of 0.2 ± 0.7 l/min for IGR and 0.0 ± 0.3 l/min for ICG (p < 0.001), respectively. There was a statistically significant difference for unphysiological circulatory conditions represented by values of 2.6-4.1 l/min and 5.6-8.6 l/min., Conclusions: Both non-invasive techniques are associated with low operating costs and require only a few expendable items for the rapid determination of cardiac function. We found an acceptable agreement between IGR and ICG as well as a high reproducibility, which was statistically significant higher for ICG. For cardiac output states exceeding the physiological range, we found a statistically significant difference. Consequently, values of cardiac function determined by either method should not be used interchangeably in the clinical setting.

Cardiac output (CO) is an important parameter for diagnosis and therapy of heart diseases, but it is still difficult to determine. Innocor, a novel noninvasive inert gas rebreathing (IGR) system, has shown promising results. However, the impact of pulmonary diseases on IGR remains unclear. The aim of the study therefore was to assess the accuracy and reliability of IGR in patients with distinct chronic lung disease. A total of 96 patients were enrolled, including 48 consecutive patients with variant lung diseases (group A) and 48 pair-matched pulmonary healthy patients (group B). CO was measured with cardiac magnetic resonance imaging (CMR) and IGR. Lung function testing was done by spirometry [FEV(1)/FVC (forced expiratory volume in one second/forced vital capacity), VC (vital capacity)] and determination of the diffusing capacity of the lung for carbon monoxide divided by alveolar volume (DLCO/VA). In group A we found a mean CO of 4.7 ± 1.3 L/min by IGR and 4.9 ± 1.2 L/min by CMR. Group B showed a mean CO of 4.8 ± 1.4 L/min by IGR and 5.0 ± 1.3 L/min by CMR. Bland-Altman analysis revealed good correspondence between CMR and IGR, with an average deviation of 0.1 ± 1.0 L/min in group A and 0.1 ± 1.0 L/min in group B (p = 0.99). Multiple regression analysis for the pulmonary parameters did not show a statistically significant impact on the mean bias of CO measurements (FEV(1)/FVC: r = 0.01, p = 0.91; VC: r = -0.2, p = 0.13; and DLCO/VA: r = 0.04, p = 0.82). IGR allows a feasible determination of CO even in patients with lung diseases. The accuracy of the IGR method is not influenced by either pulmonary obstructive and restrictive diseases or a reduced DLCO.

Background: USCOM, a novel continuous wave Doppler (CWD) device, has been introduced for noninvasive determination of cardiac output (CO). The present study aimed to compare the accuracy and reproducibility of the new device, using cardiovascular magnetic resonance imaging (CMR) as the noninvasive gold standard., Methods and Results: The CO of 56 consecutive patients was prospectively determined by CWD either before or after CMR imaging. The CWD probe was placed in the suprasternal or supraclavicular notch aiming at the aortic valve. Valid CWD signals could be obtained in 45 patients yielding a CO of 5.3+/-1.1 L/min (range, 3.0-7.5 L/min) by CMR and 4.7+/-1.1 L/min by CWD (2.5-8.0 L/min, P = .004), respectively. CWD measurements showed an acceptable agreement with CMR (bias: 0.6+/-1.1 L/min) and a high reproducibility (bias: 0.1+/-0.4 L/min). Higher CO and body mass index (BMI) were identified as sources of inaccuracy in univariate analysis. By multivariate analysis, only CO(CMR) was found to be independently associated with larger variation. Estimated diameters of the left ventricular outflow tract (LVOT), a prerequisite for CO measurement by CWD, correlated only weakly with those measured by CMR., Conclusions: Continuous wave Doppler is a feasible technique for measuring cardiac function. Although the overall agreement with CMR was acceptable, CWD showed a trend to underestimate CO. The estimated LVOT diameter by CWD is likely to be an important source of error. Nevertheless, the CWD device could be of clinical use especially for detection of intraindividual hemodynamic changes since a high reproducibility could be demonstrated., (Copyright 2010 Wiley Periodicals, Inc.)

Background: An easy, noninvasive and accurate technique for measuring cardiac output (CO) would be desirable for the diagnosis and therapy of cardiac diseases. Innocor, a novel inert-gas-rebreathing (IGR) system, has shown promising results in smaller studies. An extensive evaluation in a larger, less homogeneous patient collective is lacking., Methods: We prospectively assessed the accuracy and reproducibility of CO measurements obtained by IGR in 305 consecutive patients as compared to the noninvasive gold standard, cardiovascular magnetic resonance (CMR) imaging., Results: Bland-Altman analysis showed a good correspondence of the two methods for CO measurement with an average deviation of 0.2 +/- 1.0 liters/min (mean +/- SD) and a good reproducibility with a mean bias of 0.2 +/- 0.5 liters/min. The accuracy of the present measurements at rest was significantly better in the physiological range than in higher or lower CO ranges. The error levels set forth by current recommendations were exceeded., Conclusion: The data show that IGR measurements are easy to perform and show good agreement with CMR; however, the technique appears to be less accurate in extreme CO ranges at rest. The clinical importance of the IGR method remains to be proven by further studies.

Unlabelled: The aim of the present study was the comparison of calculated and measured values of the energy expenditure of critically ill patients during the different phases of therapeutic mild hypothermia., Patients and Methods: Five patients (mean age 40.6 years, range 23 to 68 years, 2 females) suffering from severe acute cerebral injuries who underwent mild hypothermia were prospectively included into the study. Indirect calorimetry measurements were made at intervals of 3-4 hours and subsequently, during the steady state, at least every 12 hours. The results were compared with the basal metabolic rate calculated by the Harris-Benedict equation., Results: A close linear correlation between body temperature and basal metabolism could be observed across a wide range of temperatures from 30.5 degrees C to 38.3 degrees C (r=0.82, p<0.001). One degree drop in temperature led to a 5.9% reduction in energy. During mild hypothermia, oxygen consumption was reduced by 71 mL/min (95% confidence interval 57 to 86 mL/min; p<0.001) as compared to base line. The basal metabolism rate was decreased by 30.3% (95% confidence interval 24.7 to 35.9%, p<0.001). The average value recorded was 16.7% below the values calculated in accordance with the Harris-Benedict equation (95% confidence interval 12.8 to 20.6%)., Conclusion: The immediate reduction in oxygen requirements achieved by hypothermia is linearly correlated with the reduction in temperature and the hypothermia induced reduction in oxygen requirement recorded by indirect calorimetry is considerably below that calculated in accordance with the Harris-Benedict equation. If indirect calorimetry should not be available and the Harris-Benedict equation is used, a corrective factor is therefore needed to avoid an inaccurate calorie administration.