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Background Lung emphysema is an important phenotype of chronic obstructive pulmonary disease (COPD), and CT scanning is strongly recommended to establish the diagnosis. This study aimed to identify criteria by which physicians with limited technical resources can improve the diagnosis of emphysema. Methods We studied 436 COPD patients with prospective CT scans from the COSYCONET cohort. All items of the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale, as well as data from spirometry and CO diffusing capacity, were used to construct binary decision trees. The importance of parameters was checked by the Random Forest and AdaBoost machine learning algorithms. Results When relying on questionnaires only, items CAT 1 & 7 and SGRQ 8 & 12 sub-item 3 were most important for the emphysema- versus airway-dominated phenotype, and among the spirometric measures FEV1/FVC. The combination of CAT item 1 (≤ 2) with mMRC (> 1) and FEV1/FVC, could raise the odds for emphysema by factor 7.7. About 50% of patients showed combinations of values that did not markedly alter the likelihood for the phenotypes, and these could be easily identified in the trees. Inclusion of CO diffusing capacity revealed the transfer coefficient as dominant measure. The results of machine learning were consistent with those of the single trees. Conclusions Selected items (cough, sleep, breathlessness, chest condition, slow walking) from comprehensive COPD questionnaires in combination with FEV1/FVC could raise or lower the likelihood for lung emphysema in patients with COPD. The simple, parsimonious approach proposed by us might help if diagnostic resources regarding respiratory diseases are limited. Trial registration ClinicalTrials.gov, Identifier: NCT01245933, registered 18 November 2010, https://clinicaltrials.gov/ct2/show/record/NCT01245933. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-021-01837-2.

Aims Dynamic retinal vessel analysis (DVA) provides a noninvasive way to asses microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and to identify corresponding response alterations. Methods and results We adopted a workflow consisting of noise reduction and extraction of independent components within DVA signals. Predictor performance was assessed in survival random forest models. Applying our technique to the prediction of all-cause mortality in a cohort of 214 hemodialysis patients resulted in the selection of a component which was highly correlated to maximal venous dilation following flicker stimulation (vMax), a previously identified predictor, confirming the validity of our approach. When fitting for CV mortality as the outcome of interest, a combination of three components derived from the arterial signal resulted in a marked improvement in predictive performance. Clustering analysis suggested that these independent components identified groups of patients with substantially higher CV mortality. Conclusions Our results provide a machine learning workflow to improve the predictive performance of DVA and identify groups of hemodialysis patients at high risk of CV mortality. Our approach may also prove to be promising for DVA signal analysis in other CV disease states. Translational perspective DVA is a noninvasive technique which can help to assess microvascular dysfunction, one of the driving factors of CV disease. This study demonstrates a machine learning method which improves DVA interpretation for the estimation of CV risk in hemodialysis patients. Similar techniques can help doctors to identify high risk patients for timely therapeutic interventions and to monitor the effects of these interventions.

Background After the ‘first wave’ in spring 2020, opinions regarding the threat and measures against COVID-19 seemed to vary among German general practitioners (GPs). Objectives To systematically investigate opinions and to identify subgroups of GPs sharing similar views. Methods A questionnaire was sent to all 210 practices accredited for undergraduate teaching of family medicine at the Medical Faculty of the Technical University of Munich. Questions addressed personal opinions regarding risks, dilemmas, restrictions and their relaxation associated with COVID-19, and personal fears, symptoms of depression and anxiety. Patterns of strong opinions (‘archetypes’) were identified using archetypal analysis, a statistical method seeking extremal points in the multidimensional data. Results One hundred and sixty-one GPs sent back a questionnaire (response rate 77%); 143 (68%) with complete data for all 38 relevant variables could be included in the analysis. We identified four archetypes with subgroups of GPs tending in the direction of these archetypes: a small group of ‘Sceptics’ (n = 12/8%) considering threats of COVID-19 as overrated and measures taken as exaggerated; ‘Hardliners’ (n = 34/24%) considering threats high and supporting strong measures; ‘Balancers’ (n = 77/54%) who also rated the threats high but were more critical about potentially impairing the quality of life of elderly people and children; and ‘Anxious’ GPs (n = 20/14%) tending to report more fear, depressive and anxiety symptoms. Conclusion Among the participants in this survey, opinions regarding the threat and the measures taken against COVID-19 during the ‘first wave’ in Germany in spring 2020 varied greatly.

Background: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention. Methods: In this prespecified subgroup analysis, we included 1653 patients with ST-segment–elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization. Results: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95–1.82]; P =0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P =0.83), stroke (1.3% versus 1.0%; P =0.46), and definite stent thrombosis (1.8% versus 1.0%; P =0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18–3.23]; P =0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80–1.87]; P =0.36). Conclusions: In patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

Objective Ward rounds are an essential part of physicians' daily routine. Existing studies suggest that their practical implementation is inconsistent. Therefore, developing interventions to train ward round competence and assessing if they are effective educational tools are crucial goals for research. Methods We analysed a simulation-based tutorial dedicated to fourth-year medical students, including casework and ward round simulation. We investigated the effectiveness of this intervention regarding ward round competence through a randomized controlled trial. Performance was assessed with the modified/validated surgical ward round assessment tool by two blinded and trained raters. Supplementary, motivation during the ward round tutorial was assessed for all students at different time points. Results Analysis of the ratings show that, in contrast to the control group (pre: 66.1 vs. post: 64.8 points, p = 0.72), the ward round competence of the intervention group (pre: 62.6 vs. post: 69.6 points, p = 0.0169) improved significantly after participating in the ward round tutorial. Conclusion The results show that our simulation-based training is an effective way to improve competence of medical students in conducting surgical ward rounds. Practice implications Participation in ward round trainings is a valuable tool to prepare students for their future professional practise.

Cardiac output (CO) is a key hemodynamic variable that can be minimally invasively estimated by pulse wave analysis. Multi-beat analysis is a novel pulse wave analysis method. In this prospective observational clinical method comparison study, we compared CO estimations by multi-beat analysis with CO measured by intermittent pulmonary artery thermodilution (PATD) in adult patients treated in the intensive care unit (ICU) after off-pump coronary artery bypass surgery (OPCAB). We included patients after planned admission to the ICU after elective OPCAB who were monitored with a radial arterial catheter and a pulmonary artery catheter. At seven time points, we determined CO using intermittent PATD (PATD-CO; reference method) and simultaneously recorded the radial arterial blood pressure waveform that we later used to estimate CO using multi-beat analysis (MBA-CO; test method) with the Argos monitor (Retia Medical; Valhalla, NY, USA). Blood pressure waveforms impaired by inappropriate damping properties or artifacts were excluded. We compared PATD-CO and MBA-CO using Bland–Altman analysis accounting for repeated measurements, the percentage error, and the concordance rate derived from four-quadrant plot analysis (15% exclusion zone). We analyzed 167 CO values of 31 patients. Mean PATD-CO was 5.30 ± 1.22 L/min and mean MBA-CO was 5.55 ± 1.82 L/min. The mean of the differences between PATD-CO and MBA-CO was 0.08 ± 1.10 L/min (95% limits of agreement: − 2.13 L/min to + 2.29 L/min). The percentage error was 40.7%. The four-quadrant plot-derived concordance rate was 88%. CO estimation by multi-beat analysis of the radial arterial blood pressure waveform (Argos monitor) shows reasonable agreement compared with CO measured by intermittent PATD in adult patients treated in the ICU after OPCAB.

Pulse wave analysis enables stroke volume to be estimated from an arterial blood pressure waveform. Multi-beat analysis is a novel pulse wave analysis method. We aimed to investigate cardiac output (CO) estimations using multi-beat analysis of the radial arterial blood pressure waveform in patients undergoing off-pump coronary artery bypass surgery (OPCAB) using intermittent pulmonary artery thermodilution (PATD) as the reference method. This was a prospective clinical method comparison study. In 58 patients, we measured CO using PATD (PATD-CO; reference method) and simultaneously recorded the radial arterial blood pressure waveform that we used for off-line estimation of CO based on multi-beat analysis (MBA-CO; test method) using the Argos CO monitor (Retia Medical; Valhalla, NY, USA). The final analysis was performed using 572 paired CO measurements. We performed Bland–Altman analysis accounting for multiple observations per patient. To describe the ability of the test method to track changes in CO over time we computed four-quadrant plots using a central exclusion zone of 15% and calculated the concordance rate. Mean PATD-CO was 4.13 ± 1.26 L/min and mean MBA-CO was 4.31 ± 1.25 L/min. The mean of the differences between PATD-CO and MBA-CO was − 0.20 L/min with a standard deviation of ± 1.14 L/min and 95% limits of agreement of − 2.48 to + 2.08 L/min. The concordance rate for CO changes between PATD-CO and MBA-CO was 89%. CO estimations using multi-beat analysis (Argos monitor) show reasonable agreement and trending ability compared with PATD-CO as the reference method in adult patients during OPCAB.

Objectives The purpose of the study was to investigate the impact of oral anticoagulation (OAC) type on clinical outcomes 1 year after transcatheter aortic valve replacement (TAVR). Background Non–vitamin K oral anticoagulants (NOACs) are superior to vitamin K antagonists (VKAs) in nonvalvular atrial fibrillation (AF), while their comparative performance among patients in need of OAC undergoing TAVR is underinvestigated. Methods The study enrolled 962 consecutive patients who underwent TAVR in 4 tertiary European centers and were discharged on either NOACs (n = 326) or VKAs (n = 636). By using propensity scores for inverse probability of treatment weighting (IPTW), the comparison of treatment groups was adjusted to correct for potential confounding. Results Mean age and Society of Thoracic Surgeons score of the population were 81.3 ± 6.3 years and 4.5% (interquartile range: 3.0% to 7.3%); 52.5% were women and a balloon-expandable valve was used in 62.7% of cases. The primary outcome of interest, combined incidence of all-cause mortality, myocardial infarction, and any cerebrovascular event at 1-year after TAVR, was 21.2% with NOACs versus 15.0% with VKAs (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.00 to 2.07; p = 0.050, IPTW-adjusted). The 1-year incidence of any Bleeding Academic Research Consortium bleeds and all-cause mortality were comparable between the NOAC and VKA groups, 33.9% versus 34.1% (HR: 0.97; 95% CI: 0.74 to 1.26; p = 0.838, IPTW-adjusted) and 16.5% versus 12.2% (HR: 1.36; 95% CI: 0.90 to 2.06; p = 0.136, IPTW-adjusted), respectively. Conclusions Chronic use of both NOACs and VKAs among patients in need of OAC after TAVR are comparable regarding 1-year bleeding risk. The higher ischemic event rate observed with NOACs needs to be evaluated in large randomized trials.

BACKGROUND AND AIM In contrast to the first peak of multi-organ failure in acute pancreatitis, the second peak is mostly triggered by septic complications. Our aim was to analyze the spectrum of pathogens and antimicrobial resistance development in relation to the time-course of the disease and its clinical outcome. METHODS One hundred twenty-two patients with acute necrotizing pancreatitis undergoing pancreas puncture at two tertiary academic medical centers in Germany were retrospectively analyzed. RESULTS At species level, there was a change in spectrum from Enterococcus faecalis (∆d150 - d1 = 14.6% - 16.7% = -2.1%) to Enterococcus faecium (∆d150 - d1 = 93.1% - 16.3% = 76.8%) (P

Objectives To assess the ability of multislice detector computed tomography (MDCT) to differentiate old versus acute/subacute vertebral fractures (VF) and to identify characteristic MDCT imaging signs. Methods 74 consecutive patients demonstrated 192 VF that were classified as either acute/subacute or old based on magnetic resonance imaging, MDCT, and clinical information as reference standard. Classification as acute/subacute versus old fractures based on MDCT alone was evaluated on a Likert scale by 2 independent radiologists. Morphologic MDCT features of fractures, such as trabecular compaction or fracture line, were recorded. Receiver operating characteristic analyses and Cohen's κ were used to assess the discriminatory power of the MDCT and interrater agreement, respectively. Results Out of all 192 VF, 148 fractures were acute/subacute and 44 were old according to the reference standard. Receiver operating characteristic analyses of sole MDCT assessment showed very good identification of acute/subacute VF, with areas under the curve of 0.854 and 0.861 for readers 1 and 2, respectively. When indeterminate findings were treated as acute/subacute fractures, sensitivity and specificity were 97.2% and 58.1% for reader 1 and 94.5% and 65.1% for reader 2. Interrater agreement regarding fracture age was good (weighted Cohen's κ = 0.607). Trabecular compression/callus distinct from the cortex (double compaction sign) was present in approximately half of acute/subacute VF and highly specific for acute/subacute VF (specificity = 93.2% and 88.6% for readers 1 and 2, respectively). Conclusion The acuity of VF can be assessed by MDCT alone with high sensitivity and in case of a double compaction sign with high specificity.

Postinduction and intraoperative hypotension are associated with organ injury in non-cardiac surgery patients. Automated ambulatory blood pressure monitoring can identify chronic arterial hypertension and nocturnal blood pressure non-dipping. We tested the hypotheses that: a) chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension; and b) adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information.Prediction model development based on a secondary analysis of a prospective observational study.German university medical center.366 non-cardiac surgery patients who had preoperative automated ambulatory blood pressure monitoring.Multivariable analyses to identify risk factors for postinduction and intraoperative hypotension. Area under receiver operating characteristics curves (AUROC) and likelihood-ratio tests to test whether adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information.Risk factors for postinduction hypotension were age in years (odds ratio: 1.06 (95% confidence interval: 1.03 to 1.10), P = 0.001), American Society of Anesthesiologists physical status class (1.85 (1.02 to 3.35), P = 0.043), preoperative use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (15.19 (1.76 to 131.46), P = 0.013), chronic arterial hypertension (2.54 (1.49 to 4.34), P = 0.001), and nocturnal non-dipping (3.61 (2.09 to 6.23), P 0.001). The model's AUROC was 0.76 (95% confidence interval: 0.71 to 0.81) with and 0.67 (0.62 to 0.73) without information on chronic arterial hypertension and nocturnal non-dipping (P 0.001). Risk factors for intraoperative hypotension were male sex (1.73 (1.07 to 2.80), P = 0.025), chronic arterial hypertension (4.35 (2.33 to 8.14), P 0.001), and nocturnal non-dipping (3.56 (2.07 to 6.11), P 0.001). The model's AUROC was 0.76 (0.70 to 0.81) with and 0.63 (0.57 to 0.69) without information on chronic arterial hypertension and nocturnal non-dipping (P 0.001).Chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension in non-cardiac surgery patients. Adding information on chronic arterial hypertension and nocturnal non-dipping moderately improved hypotension prediction models based on preoperative clinical information.

Background The Cancer Genome Atlas (TCGA) consortium described EBV positivity(+), high microsatellite instability (MSI-H), genomic stability (GS) and chromosomal instability (CIN) as molecular subtypes in gastric carcinomas (GC). We investigated the predictive and prognostic value of these subtypes with emphasis on CIN in the context of neoadjuvant chemotherapy (CTx) in GC. Methods TCGA subgroups were determined for 612 resected adenocarcinomas of the stomach and gastro-oesophageal junction (291 without, 321 with CTx) and 143 biopsies before CTx. EBV and MSI-H were analysed by standard assays. CIN was detected by multiplex PCRs analysing 22 microsatellite markers. Besides the TCGA classification, CIN was divided into four CIN-subgroups: low, moderate, substantial, high. Mutation profiling was performed for 52 tumours by next-generation sequencing. Results EBV(+) (HR, 0.48; 95% CI, 0.23–1.02), MSI-H (HR, 0.56; 95% CI, 0.35–0.89) and GS (HR, 0.72; 95% CI, 0.45–1.13) were associated with increased survival compared to CIN in the resected tumours. Considering the extended CIN-classification, CIN-substantial was a negative prognostic factor in uni- and multivariable analysis in resected tumours with CTx (each p p = 0.026), but was not prognostically relevant. Conclusion A refined CIN classification reveals tumours with different biological characteristics and potential clinical implications.

Importance It is unclear whether ticagrelor or prasugrel hydrochloride is superior for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Objective To assess the safety and efficacy of ticagrelor vs prasugrel for patients with ACS treated with PCI. Design, Setting, and Participants A prespecified analysis was performed of a postrandomization subgroup of 3377 patients who presented with ACS and were treated with PCI in the investigator-initiated, multicenter, phase 4, open-label Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5 randomized clinical trial, conducted from September 1, 2013, to February 28, 2018. Statistical analysis was performed from September 1, 2020, to January 30, 2021. Analysis was performed according to the intention-to-treat principle. Interventions Patients were randomly assigned to a ticagrelor-based or prasugrel-based strategy. This analysis focuses on the subgroup of patients who underwent PCI that was formed after randomization. Main Outcomes and Measures The primary end point was a composite consisting of all-cause death, myocardial infarction, or stroke at 12 months. The safety end point was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Results The ticagrelor group comprised 1676 patients (1323 men [78.9%]; mean [SD] age, 64.4 [12.0] years), and the prasugrel group comprised 1701 patients (1341 men [78.8%]; mean [SD] age, 64.7 [12.0] years). The primary end point occurred for 162 patients (9.8%) in the ticagrelor group and 120 patients (7.1%) in the prasugrel group (hazard ratio [HR], 1.41; 95% CI, 1.11-1.78;P = .005). Myocardial infarction occurred in 88 patients (5.3%) in the ticagrelor group compared with 55 patients (3.8%) in the prasugrel group (HR, 1.67; 95% CI, 1.19-2.34;P = .003). The safety end point, BARC type 3 to 5 bleeding, occurred in 84 of 1672 patients (5.3%) in the ticagrelor group and 78 of 1680 patients (4.9%) in the prasugrel group (HR; 1.10; 95% CI, 0.81-1.50;P = .54). Conclusions and Relevance Among patients presenting with ACS who were treated with PCI, the incidence of the primary composite end point occurred less frequently for patients who received prasugrel compared with those who received ticagrelor. The incidence of bleeding events was comparable between the 2 groups. These results suggest that, for patients presenting with ACS who undergo PCI, a prasugrel-based strategy is superior to a ticagrelor-based strategy. However, because these observations are based on a postrandomization subgroup, these findings should be regarded as hypothesis generating and dedicated randomized clinical trials may be warranted to confirm these findings. Trial Registration ClinicalTrials.gov Identifier:NCT01944800

Importance The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant. Objective To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI. Design, Setting, and Participants A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI). Interventions Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy. Main Outcomes and Measures The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days. Results Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5′-diphosphate–induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36). Conclusions and Relevance Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms. Trial Registration ClinicalTrials.gov Identifier:NCT03312855

Background Risk factors of severe COVID-19 have mainly been investigated in the hospital setting. We investigated pre-defined risk factors for testing positive for SARS-CoV-2 infection and cardiovascular or pulmonary complications in the outpatient setting. Methods The present cohort study makes use of ambulatory claims data of statutory health insurance physicians in Bavaria, Germany, with polymerase chain reaction (PCR) test confirmed or excluded SARS-CoV-2 infection in first three quarters of 2020. Statistical modelling and machine learning were used for effect estimation and for hypothesis testing of risk factors, and for prognostic modelling of cardiovascular or pulmonary complications. Results A cohort of 99 811 participants with PCR test was identified. In a fully adjusted multivariable regression model, dementia (odds ratio (OR) = 1.36), type 2 diabetes (OR = 1.14) and obesity (OR = 1.08) were identified as significantly associated with a positive PCR test result. Significant risk factors for cardiovascular or pulmonary complications were coronary heart disease (CHD) (OR = 2.58), hypertension (OR = 1.65), tobacco consumption (OR = 1.56), chronic obstructive pulmonary disease (COPD) (OR = 1.53), previous pneumonia (OR = 1.53), chronic kidney disease (CKD) (OR = 1.25) and type 2 diabetes (OR = 1.23). Three simple decision rules derived from prognostic modelling based on age, hypertension, CKD, COPD and CHD were able to identify high risk patients with a sensitivity of 74.8% and a specificity of 80.0%. Conclusions The decision rules achieved a high prognostic accuracy non-inferior to complex machine learning methods. They might help to identify patients at risk, who should receive special attention and intensified protection in ambulatory care.

OBJECTIVES: The objective of the study is to determine the impact of changing reference standards (RS), namely spirometry vs. whole-body plethysmography (WBP), on estimation of the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) and clinical signs and symptoms (CSS) as index tests regarding asthma diagnosis. STUDY DESIGN AND SETTING: This was a diagnostic study conducted in 393 patients attending a private practice of pneumologists with complaints suspicious of asthma. First, the index tests were compared with the diagnostic results of spirometry in terms of forced expiratory volume in the first second (FEV1) responsiveness. Second, the index tests were compared with the results of WBP in terms of specific airway resistance and FEV1 responsiveness. Areas under the curve (AUC) were compared with a generalized estimating equation approach based on binary logistic regression. RESULTS: FeNO values and CSS 'wheezing' and 'allergic rhinitis' showed higher specificities (P

Background The efficacy and safety of a reduced dose of prasugrel versus a standard dose of ticagrelor in elderly patients or those with a low body weight presenting with an acute coronary syndrome (ACS) are unknown. Objective To investigate the effect of an age- and weight-adapted dose of prasugrel versus a standard dose of ticagrelor in patients with ACS. (ClinicalTrials.gov: NCT01944800). Design Prespecified analysis of the multicenter, randomized ISAR-REACT 5 trial. Setting 23 centers in Germany and Italy. Patients 3997 patients with ACS planned for invasive management. Intervention Participants were randomly assigned to receive a standard dose of ticagrelor or prasugrel (reduced dose in the elderly or low-weight group and standard dose in the neither elderly nor low-weight group). Measurements The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months. Results In the elderly or low-weight group, the efficacy end point occurred in 12.7% of patients assigned to receive prasugrel and 14.6% of those assigned to receive ticagrelor (hazard ratio [HR], 0.82 [95% CI, 0.60 to 1.14]); in the neither elderly nor low-weight group, the efficacy end point occurred in 4.8% of patients assigned to receive prasugrel and 7.3% of those assigned to receive ticagrelor (HR, 0.65 [CI, 0.48 to 0.88]; P for interaction > 0.2). In the elderly or low-weight group, Bleeding Academic Research Consortium type 3 to 5 bleeding occurred in 8.1% of patients assigned to receive prasugrel and 10.6% of those assigned to receive ticagrelor (HR, 0.72 [0.46 to 1.12]), and in 3.7% and 3.8%, respectively, of patients in the neither elderly nor low-weight group (HR, 0.98 [CI, 0.65 to 1.47]; P for interaction > 0.2). Limitation The study is a subgroup analysis. Conclusion In elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk for bleeding. Primary funding source German Center for Cardiovascular Research and Deutsches Herzzentrum Munchen.

Introduction In mice there might be an association between sleep deprivation and amyloid β plasma levels. Hence, we examined whether amyloid plasma levels are associated with sleep duration or fragmentation in 17 psychiatrists on-call. Methods Amyloid β (Aβ)42, Aβ40, and soluble amyloid precursor protein β (sAPP-β) plasma concentrations were measured at the beginning and end of 90 on-call nights, and analyzed using generalized linear models. Results In on-call nights, a 10.7% reduction of Aβ42 was revealed overnight. Every single short sleep interruption diminished this reduction by 5.4%, as well as every pg/mL of sAPP-β by 1.2%, each copy of APOE e4 by 10.6%, and each year of professional experience by 3.0%. Discussion The extent of sleep fragmentation diminishes the physiological overnight reduction of Aβ42 but not Aβ40 plasma levels in the same direction as the enzyme for Aβ42 production, the genetic risk factor for Alzheimer's disease (AD), and on-call experience. Might on-call duty and sleep fragmentation in general alter the risk for AD?

Introduction and aims. We aimed to explore the impact of infection diagnosed upon admission and of other clinical baseline parameters on mortality of cirrhotic patients with emergency admissions. Material and methods. We performed a prospective observational monocentric study in a tertiary care center. The association of clinical parameters and established scoring systems with short-term mortality up to 90 days was assessed by univariate and multivariable Cox regression analysis. Akaike’s Information Criterion (AIC) was used for automated variable selection. Statistical interaction effects with infection were also taken into account. Results. 218 patients were included. 71.2% were male, mean age was 61.1 ± 10.5 years. Mean MELD score was 16.2 ± 6.5, CLIF-consortium Acute on Chronic Liver Failure-score was 34 ± 11. At 28, 90 and 365 days, 9.6%, 26.0% and 40.6% of patients had died, respectively. In multivariable analysis, respiratory organ failure [Hazard Ratio (HR) = 0.15], albumin substitution (HR = 2.48), non-HCC-malignancy (HR = 4.93), CLIF-C-ACLF (HR = 1.10), HCC (HR = 3.70) and first episode of ascites (HR = 0.11) were significantly associated with 90-day mortality. Patients with infection had a significantly higher 90-day mortality (36.3 vs. 20.1%, p = 0.007). Cultures were positive in 32 patients with resistance to cephalosporins or quinolones in 10, to ampicillin/sulbactam in 14 and carbapenems in 6 patients. Conclusion. Infection is common in cirrhotic ED admissions and increases mortality. The proportion of resistant microorganisms is high. The predictive capacity of established scoring systems in this setting was low to moderate.

Magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is an excellent tool for diagnosing intracranial infection, with limitations in previous neurosurgical intervention. This study aimed to evaluate the accuracy of DWI in the diagnosis of postoperative intracranial infection.We retrospectively evaluated all consecutive patients with intracranial infection undergoing a neurosurgical intervention who had preoperative MRI, including DWI. Patients were divided into 2 groups: spontaneous intracranial infection (SI) and postoperative intracranial infection (PI). A control group (CG) of patients who had undergone brain surgery without any signs of subsequent infection was also included. Qualitatively, MRI data were evaluated for the presence of intracranial infection. Sensitivity, specificity, and positive and negative predictive values for PI as opposed to no infection were determined. Quantitatively, areas with diffusion restriction within the surgery/abscess cavity were identified for the 3 groups using semiautomated segmentation. Group differences regarding apparent diffusion coefficient (ADC) ratios were evaluated. Receiver operating characteristic curve analysis was used to identify a point in time beyond which ADC ratios might show reasonable discriminatory power between the PI and CG groups.A total of 78 patients were included (38 in the SI group, 20 in the PI group, 20 in the CG group). Sensitivity, specificity, and positive and negative predictive values in the diagnosis of PI were 80%, 95%, 4%, and 100%, respectively. Median ADC was significantly higher in the PI group compared with the SI group (0.98 vs. 0.69; P0.001) but lower compared with the CG group (1.24; P = 0.16). The analysis suggested a possible differentiation of PI and CG after a time interval of approximately 100 days/3 months.DWI is of limited value in evaluating postoperative brain infection. Our data show a trend toward DWI regaining its validity at approximately 3 months after surgery.

Background Use of a side-viewing endoscope is currently mandatory to examine the major duodenal papilla; however, previous studies have used cap-assisted endoscopy for complete examination of the papilla. The aim of this study was to compare cap-assisted endoscopy with side-viewing endoscopy for examination of the major duodenal papilla. Methods This was a prospective, randomized, blinded, controlled, noninferiority crossover study. Patients were randomized to undergo either side-viewing endoscopy followed by cap-assisted endoscopy or cap-assisted endoscopy followed by side-viewing endoscope. Photographs of the major duodenal papilla were digitally edited to mask the cap area before they were evaluated by three blinded external examiners. Our primary end point was complete visualization of the major duodenal papilla. Secondary end points were the ability to examine the mucosal pattern, the overview of the periampullary region, overall satisfaction, and time to locate the papilla. Results 62 patients completed the study. Complete visualization of the major duodenal papilla was achieved in 60 examinations by side-viewing endoscopy and in 59 by cap-assisted endoscopy (97 % vs. 95 %). The difference between the two examinations was 1.6 % with a two-sided 95 % confidence interval of −4.0 % to 7.3 %, which did not exceed the noninferiority margin of 8 %. Cap-assisted endoscopy achieved better scores regarding the examination of mucosal pattern and overall satisfaction, whereas side-viewing endoscopy had a better overview score (P Conclusion Cap-assisted endoscopy and side-viewing endoscopy had similar success rates for complete visualization of the major duodenal papilla. Cap-assisted endoscopy is superior to side-viewing endoscopy regarding the mucosal pattern and overall satisfaction. Side-viewing endoscopy gives a better overview of the periampullary region.

Aims We sought to determine the long-term outcome of high-risk patients who underwent transcatheter aortic valve replacement (TAVR) with first-generation devices with a focus on the identification of predictors for mortality and valve durability. Methods and results Consecutive patients in our prospective single-centre registry undergoing TAVR with first-generation devices (n=214 CoreValve; n=86 SAPIEN) between 06/2007 and 07/2009 were retrospectively analysed (n=300, mean age 81.43±6.55 years, mean STS score 6.5±4.5%). Kaplan-Meier estimates of survival and the Cox proportional hazards model were used to identify independent predictors of all-cause-mortality. At 1, 5, and 7 years, estimated survival rates were 76.0%, 40.2%, and 23.2%, respectively. Age-adjusted baseline predictors of mortality included atrial fibrillation, impaired kidney function, peripheral artery disease, and mitral regurgitation (≥moderate). Baseline risk-adjusted procedure-related predictors for all-cause mortality included acute kidney injury, neurological events, major vascular complications, and major/life-threatening bleeding. At both five and six years, 78.2% of surviving patients were in NYHA Class I or II. PVL was ≤mild in the majority of patients at discharge and throughout follow-up. At seven years, the overall crude cumulative incidence of structural valve deterioration according to the 2017 EAPCI/ESC/EACTS definition was 14.9% (CoreValve 11.8% vs. SAPIEN 22.6%; p=0.01). Conclusions Seven years after TAVR, 23.2% of high-risk patients were still alive. Independent predictors of all-cause mortality included both patient- and procedure-related factors. With a cumulative incidence of 14.9% at seven years, there is some suggestion that SVD post TAVR may become increasingly relevant during longer-term follow-up.

Different sedation regimens have been described for use during transfemoral transcatheter aortic valve implantation (tf-TAVI) for treatment in patients with severe aortic stenosis. The purpose of this study was to compare dexmedetomidine (DEX) with a combination of propofol-opioid (PO) with respect to periprocedural gas exchange and hemodynamic support. Data from a cohort of patients sedated with either DEX or PO for tf-TAVI were retrospectively analyzed from a prospectively maintained TAVI registry. Operative risk was determined from comorbidities and risk scores. Periprocedural partial pressure of carbon dioxide (PaCO2) was chosen as the primary endpoint. Other differences in gas exchange, need for catecholamine therapy, the frequency of conversion to general anesthesia, and need for sedative “rescue therapy” (in DEX patients) were secondary endpoints. Inverse probability of treatment weighting (IPTW) was used for analysis to minimize any selection bias. Of the 297 patients (140 PO, 157 DEX) included, the median [interquartile range] periprocedural PaCO2 values of DEX patients were significantly lower than in PO patients (40 [36-45] mmHg vs 44 [40-49] mmHg, respectively; median difference −4 mmHg; 95% confidence interval, −5 to −3 mmHg; P 45 mmHg) was significantly less frequent in DEX patients compared with the PO group (25% vs 42%, respectively; P = 0.005). Vasopressor support was more frequent in the PO group compared with DEX (68% vs 25%, respectively; P < 0.001). Conversion to general anesthesia was not different between groups (9%, PO vs 3%, DEX; P = 0.051). Additional sedatives/opioids were required in 25 (16%) of the DEX patients. In sedated TAVI patients, DEX was associated with lower PaCO2 values and reduced requirements for vasopressor support, making it a promising alternative to PO for sedation during TAVI. www.ClinicalTrials.gov (NCT01390675). Registered 11 July 2011.

The aim of this investigation was to identify patient's characteristics and periprocedural variables related to periprocedural transfusion in transfemoral Transcatheter Aortic Valve Implantation (tf-TAVI).Transfusion of allogenic red-blood cells (RBC) in tf-TAVI and the number of transfused units has been linked to an increased 30-day mortality. In line with the trend of minimization and cost-effectiveness, transfusion should be avoided, wherever possible.Between 2007 and 2015, 1,734 procedures were analyzed from our prospective registry for RBC-transfusion. Multiple logistic regression analysis was used to identify the dependent variables.Transfusion was considered necessary in 14% (n = 243) of the patients. Female gender (OR [95% CI]) (1.680 [1.014-2.783]) and preprocedural moderate (7.594 [4.404-13.095]) and severe anemia (8.202 [0.900-74.752]) according to WHO were the most important preprocedural variables. Periprocedural, pericardial effusion (12.109 [3.753-39.063]), emergency extracorporeal circulation (54.5288 [6.178-481.259]) and major vascular injury (2.647 [1.412-4.962]) were related to transfusion. The same applies to moderate (4.255 [1.859-9.740]) and severe anemia (31.567 [8.560-116.416]) as well as periprocedural experience (0.072 [0.035-0.149] - 0.141[0.079-0.251], P 0.001) CONCLUSION: Procedural experience, serious adverse events, low pre- and periprocedural Hb levels and female gender were the main variables relating to transfusion. Even in experienced high-volume centers, transfusion is still necessary in a considerable number of patients.

BACKGROUND: Asthma education (AE) is associated with reduced hospitalization and disability. We compared the effectiveness of an electronic AE program (eAEP) with a conventional face-to-face AE program (presence-based AEP; pAEP) for asthma knowledge (AK) with regard to self-management. METHODS: A randomized controlled pilot study was conducted in a pulmonary reha- bilitation clinic. AK was determined by means of the Asthma Knowledge Test (AKT). The change in AKT score within each group was calculated with a paired t-test. Group differences were estimated with adjusted linear regression models. RESULTS: In the intervention group (n = 41), the AKT score increased from 41.57 (standard deviation 5.63) at baseline to 45.82 (3.84) after completion of the eAEP (p < 0.001), and again to 47.20 (3.78) after completion of the pAEP (p = 0.046). In the control group (n = 41), the score increased from 41.73 (4.74) at baseline to 45.72 (3.65) after completion of the pAEP (p < 0.001). There was no relevant differ- ence in knowledge gain between the eAEP and the pAEP group after completion of the corresponding educational sessions (p = 0.881). The AKT score was higher in the eAEP group after obligatory participation in pAEP than in the group that only completed the pAEP (p = 0.020). CONCLUSION: An internet-based AEP could help to reduce the knowledge deficits of a large proportion of patients with asthma.

OBJECTIVES Cryoballoon pulmonary vein isolation (cPVI) in patients with atrial fibrillation requires fluoroscopic guidance, causing a relevant amount of radiation exposure. Strategies to reduce radiation exposure in electrophysiologic procedures and specifically cPVI are of great importance. The aim of this study was to evaluate a possible reduction of radiation dose using the novel Azurion 7 F12 x-ray system compared with its predecessor Allura FD10. METHODS In February 2017, the Philips Azurion angiography system was introduced, combining the Allura Clarity radiation dose reduction technology with a more powerful generator, improved image resolution, and a large screen display. In 173 patients undergoing cPVI by a single experienced operator in our institution between December 2016 and April 2018, dose area products (cGy×cm) and image quality were compared using Azurion 7 F12 or Allura FD10 angiography system. RESULTS A significant reduction in total radiation dose expressed as a dose area products of 524 (332; 821) cGy×cm on the Allura system compared with 309 (224; 432) cGy×cm on the Azurion system was observed (P

ObjectiveTo investigate whether immune cell composition and content of neutrophil extracellular traps (NETs) in relation to clinical outcome are different between acute ischemic stroke (AIS) and acute myocardial infarction (AMI), we performed histologic analysis and correlated results with clinical and procedural parameters.MethodsWe retrieved thrombi from patients with AIS (n = 71) and AMI (n = 72) during endovascular arterial recanalization and analyzed their immune cell composition and NET content by immunohistology. We then associated thrombus composition with procedural parameters and outcome in AIS and with cardiac function in patients with AMI. Furthermore, we compared AIS thrombi with AMI thrombi and differentiated Trial of Org 10172 in Acute Stroke Treatment classifications to address potential differences in thrombus pathogenesis.ResultsAmounts of leukocytes (p = 0.133) and neutrophils (p = 0.56) were similar between AIS and AMI thrombi. Monocytes (p = 0.0052), eosinophils (p < 0.0001), B cells (p < 0.0001), and T cells (p < 0.0001) were more abundant in stroke compared with AMI thrombi. NETs were present in 100% of patients with AIS and 20.8% of patients with AMI. Their abundance in thrombi was associated with poor outcome scores in patients with AIS and with reduced ejection fraction in patients with AMI.ConclusionIn our detailed histologic analysis of arterial thrombi, thrombus composition and especially abundance of leukocyte subsets differed between patients with AIS and AMI. The presence and amount of NETs were associated with patients' outcome after AIS and AMI, supporting a critical impact of NETs on thrombus stability in both conditions.

Volumetric-modulated arc therapy (VMAT) achieves high conformity to the planned target volume (PTV) and good sparing of organs at risk (OAR). This study compares dosimetric parameters and toxicity in esophageal cancer (EC) patients treated with VMAT and 3D conformal radiotherapy (3D-CRT). Between 2007 and 2014, 17 SC patients received neoadjuvant chemoradiation (CRT) with VMAT. Dose–volume histograms and toxicity were compared between these patients and 20 treated with 3D-CRT. All patients were irradiated with a total dose of 45 Gy. All VMAT patients received simultaneous chemotherapy with cisplatin and 5‑fluorouracil (5-FU) in treatment weeks 1 and 5. Of 20 patients treated with 3D-CRT, 13 (65 %) also received CRT with cisplatin and 5‑FU, whereas 6 patients (30 %) received CRT with weekly oxaliplatin and cetuximab, and a continuous infusion of 5‑FU (OE-7). There were no differences in baseline characteristics between the treatment groups. For the lungs, VMAT was associated with a higher V5 (median 90.1 % vs. 79.7 %; p = 0.013) and V10 (68.2 % vs. 56.6 %; p = 0.014), but with a lower V30 (median 6.6 % vs. 11.0 %; p = 0.030). Regarding heart parameters, VMAT was associated with a higher V5 (median 100.0 % vs. 91.0 %; p = 0.043), V10 (92.0 % vs. 79.2 %; p = 0.047), and Dmax (47.5 Gy vs. 46.3 Gy; p = 0.003), but with a lower median dose (18.7 Gy vs. 30.0 Gy; p = 0.026) and V30 (17.7 % vs. 50.4 %; p = 0.015). Complete resection was achieved in 16 VMAT and 19 3D-CRT patients. Due to systemic progression, 2 patients did not undergo surgery. The most frequent postoperative complication was anastomosis insufficiency, occurring in 1 VMAT (6.7 %) and 5 3D-CRT patients (27.8 %; p = 0.180). Postoperative pneumonia was seen in 2 patients of each group (p = 1.000). There was no significant difference in 3‑year overall (65 % VMAT vs. 45 % 3D-CRT; p = 0.493) or 3‑year progression-free survival (53 % VMAT vs. 35 % 3D-CRT; p = 0.453). Although dosimetric differences in lung and heart exposure were observed, no clinically relevant impact was detected in either patient group. In a real-life patient cohort, VMAT enables reduction of lung and heart V30 compared to 3D-CRT, which may contribute to reduced toxicity.

The life expectancy of HIV-infected patients has recently been increasing. Although the mortality and morbidity associated with AIDS is decreasing, those associated with cardiovascular diseases and percutaneous coronary intervention (PCI) are receiving greater attention. Only limited data regarding coronary restenosis are available in these patients.In this prospective, systematic angiographic follow-up study, we enrolled HIV patients who underwent PCI for de-novo lesions and subsequent routine angiographic follow-up for 6-8 months. Angiographic restenosis was defined as stenosis of at least 50% of the in-segment area.Univariate and multivariate analyses were performed to evaluate restenosis and its predictors.Between May 2002 and March 2014, 47 patients with HIV underwent PCI in two high-volume centers in Munich, Germany. Of these patients, 41 with 131 de-novo lesions underwent invasive surveillance. One-quarter of the lesions treated subsequently presented with restenosis. Univariate analysis indicated that CD8 T-cell levels (P = 0.006), serum cholesterol (P = 0.042) and low-density lipoprotein-cholesterol (P = 0.042) levels at baseline, total number of stents (P = 0.047), and C-reactive protein level (P = 0.001) at follow-up were associated with restenosis. Multivariate analysis indicated that CD8 T-cell levels (P = 0.006) and persistent C-reactive protein elevation at 6-month follow-up (P = 0.00013) were independent predictors of restenosis.Inflammation, represented by CD8 T-cell levels, and persistent C-reactive protein elevation are independent predictors of angiographic restenosis and should therefore be closely monitored in HIV patients undergoing PCI.

Human sample, from patients or healthy donors, are a valuable link between basic research and clinic. Especially in translational research, they play an essential role in understanding development and progression of diseases as well as in developing new diagnostic and therapeutic tools. Stored in biobanks, fast access to appropriate material becomes possible. However, biobanking in a clinical context faces several challenges. In practice, collecting samples during clinical routine does not allow to strictly adhere to protocols of sample collection in all aspects. This may influence sample quality to variable degrees. Time from sample draw to asservation is a variable factor, and influences of prolonged storage at ambient temperature of tissues are not well understood. We investigated whether delays between 5 minutes and 3 hours, and the use of RNAlater RNA-preserving reagent would lead to a relevant drop in sample quality, measured by quantitative mRNA expression analysis. Our findings suggest that even under ambient conditions, delays up to 3 hours do not have a major impact on sample quality as long as the tissue remains intact.

Transcatheter aortic valve implantation (TAVI) is a treatment strategy for patients with severe aortic stenosis. Although general anaesthesia (TAVI-GA) and sedation (TAVI-S) have previously been described for TAVI, the difference in safety and efficacy of both methods has not been studied in a randomized trial.The INSERT trial was a single centre, controlled parallel-group trial with balanced randomization. Sixty-six patients (68-94 yr) with acquired aortic stenosis undergoing transfemoral CoreValve™ were assigned to TAVI-GA or TAVI-S. Comparable operative risk was determined from risk-scores (EUROscore, STS-Score). Monitoring and anaesthetic drugs were standardized. Near-Infrared-Spectroscopy was used to monitor cerebral-oxymetry blinded. Primary outcome was the perioperative cumulative cerebral desaturation. As secondary outcomes, changes in neurocognitive function and respiratory and haemodynamic adverse events were evaluated.Of 66 included patients, 62 (TAVI-GA: n=31, TAVI-S: n=31) were finally analysed. Baseline characteristics were comparable. In 24 patients (39%) cerebral desaturation was observed. Cumulative cerebral desaturation was comparable (TAVI-GA:(median [IQR]) (0[0/1308] s%) vs. TAVI-S:(0[0/276] s%); P=0.505) between the groups. Neurocognitive function did not change within and between groups. Adverse events were more frequently observed in TAVI-S patients (P0.001). Bradypnoea (n=16, 52%) and the need for airway manoeuvres (n=11, 36%) or bag-mask-ventilation (n=6, 19%) were the most common respiratory adverse events.Cerebral desaturation occurred in both patient groups, but there was no significant difference between the two groups. Based on primary outcome, both methods were shown to be comparable. Neurocognitive outcome was similar. The higher incidence of adverse events in the sedation group suggests a potential advantage of general anaesthesia.NCT 01251328.

The CNAP system allows continuous noninvasive arterial pressure measurement based on the volume clamp method using a finger cuff. We aimed to evaluate the agreement between arterial pressure measurements noninvasively obtained using the CNAP device and arterial catheter-derived arterial pressure measurements in intensive care unit patients. In 55 intensive care unit patients, we simultaneously recorded arterial pressure values obtained by an arterial catheter placed in the abdominal aorta through the femoral artery (criterion standard) and arterial pressure values determined noninvasively using CNAP. We performed Bland–Altman analysis and calculated the percentage error. The mean difference (±standard deviation, 95 % limits of agreement, percentage error) between noninvasive (CNAP) and invasively assessed arterial pressure was for mean arterial pressure +1 mmHg (±9 mmHg, −16 to +19 mmHg, 22 %), for systolic arterial pressure −10 mmHg (±16 mmHg, −42 to +21 mmHg, 27 %), and for diastolic arterial pressure +7 mmHg (±9 mmHg, −10 to +24 mmHg, 28 %). Our results indicate a reasonable accuracy and precision for the determination of mean and diastolic arterial pressure by noninvasive continuous arterial pressure measurements using the volume clamp method compared with the criterion standard (invasive arterial catheter). Systolic arterial pressure is determined less accurately and precisely.

Neurovascular coupling can be directly assessed by retinal vessel response to flickering light using optical imaging methods. The response is altered in a number of ocular and cardiovascular diseases. Whether it is altered in Alzheimer’s disease (AD) is investigated. Retinal vessel reaction to monochromatic flicker stimulation was examined by Dynamic Vessel Analyzer independent of the commercial software in elderly subjects: 15 patients with mild-to-moderate dementia due to AD (ADD); 24 patients with mild cognitive impairment due to AD (MCI); 15 cognitively healthy controls (HC). Retinal vessels in ADD showed a more emphasized and delayed reactive dilation as compared to HC. In MCI, these aspects still differed from those seen in ADD. Maximal arterial reaction was increased and dilation was delayed in ADD as compared to HC (p = 0.004 and p

Background A high percentage of closed femur fractures have slight comminution. Using micro-CT (μCT), multiple fragment segmentation is much more difficult than segmentation of unfractured or osteotomied bone. Manual or semi-automated segmentation has been performed to date. However, such segmentation is extremely laborious, time-consuming and error-prone. Our aim was to therefore apply a fully automated segmentation algorithm to determine μCT parameters and examine their association with biomechanics. Methods The femura of 64 rats taken after randomised inhibitory or neutral medication, in terms of the effect on fracture healing, and controls were closed fractured after a Kirschner wire was inserted. After 21 days, μCT and biomechanical parameters were determined by a fully automated method and correlated (Pearson’s correlation). Results The fully automated segmentation algorithm automatically detected bone and simultaneously separated cortical bone from callus without requiring ROI selection for each single bony structure. We found an association of structural callus parameters obtained by μCT to the biomechanical properties. However, results were only explicable by additionally considering the callus location. Conclusions A large number of slightly comminuted fractures in combination with therapies that influence the callus qualitatively and/or quantitatively considerably affects the association between μCT and biomechanics. In the future, contrast-enhanced μCT imaging of the callus cartilage might provide more information to improve the non-destructive and non-invasive prediction of callus mechanical properties. As studies evaluating such important drugs increase, fully automated segmentation appears to be clinically important.

Insulin resistance is the underlying mechanism for the metabolic syndrome and associated dyslipidaemia that theoretically implies a practical tool for identifying individuals at risk for cardiovascular disease and type-2-diabetes. Another screening tool is the hypertriglyceremic-waist phenotype (HTW). There is important impact of the ethnic background but a lack of studied European populations for the association of the triglyceride/high-density lipoprotein cholesterol (HDL-C) ratio and insulin resistance. This observational, retrospective study evaluated lipid ratios and the HTW for predicting the metabolic syndrome/insulin resistance in 1932 non-diabetic individuals from Germany in the fasting state and during a glucose tolerance test. The relations of triglyceride/HDL-C, total-cholesterol/HDL-C, and low-density lipoprotein cholesterol/HDL-C with 5 surrogate estimates of insulin resistance/sensitivity and metabolic syndrome were analysed by linear regression analysis and receiver operating characteristics (ROC) in participants with normal (n=1 333) or impaired fasting glucose (n=599), also for the impact of gender. Within the lipid ratios, triglyceride/HDL-C had the strongest associations with insulin resistance/sensitivity markers. In the prediction of metabolic syndrome, diagnostic accuracy was good for triglyceride/HDL-C (area under the ROC curve 0.817) with optimal cut-off points (in mg/dl units) of 2.8 for men (80% sensitivity, 71% specificity) and 1.9 for women (80% sensitivity, 75% specificity) and fair for HTW and HOMA-IR (area under the curve 0.773 and 0.761). These data suggest the triglyceride/HDL-C ratio as a physiologically relevant and practical index for predicting the concomitant presence of metabolic syndrome, insulin resistance and dyslipidaemia for therapeutic and preventive care in apparently healthy European populations.

Mortality of cirrhotic patients after emergency care admission is high, and prognostic factors can help in prioritizing patients. The aim of our study was to assess the association between levels of cardiac troponin T (cTnT) and 1-year mortality in patients with liver cirrhosis without known cardiac disease, who were admitted to the emergency department (ED).All patients with cirrhosis presented to the ED from October 2009 until August 2015 who had an initial cTnT value measured with the first lab panel were retrospectively analyzed with a follow-up of 365 days.Of a total of 237 cirrhotic ED patients, cTnT measurements were available for 87 (63% men, mean age 58.9 ± 11.0 years, and median Model for End-stage Liver Disease score was 15 [25th-75th percentile: 10-19]). Chronic Liver Failure Consortium acute-on-chronic liver failure (CLIF-C-ACLF) score was 33. Forty-three patients (49%) had cTnT values above the normal range (14 ng/L), of which 19 (22%) had values over 30 ng/L. Two patients were lost to follow-up. In multivariable analysis, both CLIF-C-ACLF (hazard ratio 1.072 per point increase; 95% confidence interval 1.029-1.117; P 0.001) and cTnT (hazard ratio 1.014 per ng/L increase; 95% confidence interval 1.004-1.024; P = 0.008) emerged as independently associated with mortality.A large proportion of cirrhotic patients in the ED have elevated levels of cTnT even if there is no evidence of cardiac disease. Elevated cTnT is associated with increased mortality during 1 year after correcting for Model for End-stage Liver Disease and CLIF-C-ACLF scores.

The sickest-first principle in donor-liver allocation can be implemented by allocating organs to patients with cirrhosis with the highest Model for End-Stage Liver Disease (MELD) scores. For patients with other risk factors, standard exceptions (SEs) and nonstandard exceptions (NSEs) have been developed. We investigated whether this system of matched MELD scores achieves similar outcomes on the liver transplant waiting list for various diagnostic groups in Eurotransplant (ET) countries with MELD-based individual allocation (Belgium, the Netherlands, and Germany). A retrospective analysis of the ET wait-list outflow from December 2006 until December 2015 was conducted to investigate the relation of the unified MELD-based allocation to the risk of a negative wait-list outcome (death on the waiting list or delisting as too sick) as opposed to a positive wait-list outcome (transplantation or delisting as recovered). A total of 16,926 patients left the waiting list with a positive (11,580) or negative (5346) outcome; 3548 patients had a SE, and 330 had a NSE. A negative outcome was more common among patients without a SE or NSE (34.3%) than among patients with a SE (22.6%) or NSE (18.6%; P < 0.001). Analysis by model-based recursive partitioning detected 5 risk groups with different relations of matched MELD to a negative outcome. In Germany, we found the following: (1) no SE or NSE, SE for biliary sepsis (BS); (2) SE for hepatocellular carcinoma (HCC), hepatopulmonary syndrome (HPS), or portopulmonary hypertension (PPH); and (3) SE for primary sclerosing cholangitis (PSC) or polycystic liver disease (PcLD). In Belgium and the Netherlands, we found the following: (4) SE or NSE, or SE for HPS or PPH; and (5) SE for BS, HCC, PcLD, or PSC. In conclusion, SEs and NSEs do not even out risks across different diagnostic groups. Patients with SEs or NSEs appear advantaged toward patients with cirrhosis without SEs or NSEs. Liver Transplantation 23 1256-1265 2017 AASLD.

Restoration of biomechanics is a major goal in THA. Imageless navigation enables intraoperative control of leg length equalization and offset reconstruction. However, the effect of navigation compared with intraoperative fluoroscopy is unclear.We asked whether intraoperative use of imageless navigation (1) improves the relative accuracy of leg length and global and femoral offset restoration; (2) increases the absolute precision of leg length and global and femoral offset equalization; and (3) reduces outliers in a reconstruction zone of ± 5 mm for leg length and global and femoral offset restoration compared with intraoperative fluoroscopy during minimally invasive (MIS) THA with the patient in a lateral decubitus position.In this prospective study a consecutive series of 125 patients were randomized to either navigation-guided or fluoroscopy-controlled THA using sealed, opaque envelopes. All patients received the same cementless prosthetic components through an anterolateral MIS approach while they were in a lateral decubitus position. Leg length, global or total offset (representing the combination of femoral and acetabular offset), and femoral offset differences were restored using either navigation or fluoroscopy. Postoperatively, residual leg length and global and femoral offset discrepancies were analyzed on magnification-corrected radiographs of the pelvis by an independent and blinded examiner using digital planning software. Accuracy was defined as the relative postoperative difference between the surgically treated and the unaffected contralateral side for leg length and offset, respectively; precision was defined as the absolute postoperative deviation of leg length and global and femoral offset regardless of lengthening or shortening of leg length and offset throughout the THA. All analyses were performed per intention-to-treat.Analyzing the relative accuracy of leg length restoration we found a mean difference of 0.2 mm (95% CI, -1.0 to +1.4 mm; p = 0.729) between fluoroscopy and navigation, 0.2 mm (95 % CI, -0.9 to +1.3 mm; p = 0.740) for global offset and 1.7 mm (95 % CI, +0.4 to +2.9 mm; p = 0.008) for femoral offset. For the absolute precision of leg length and global and femoral offset equalization, there was a mean difference of 1.7 ± 0.3 mm (p0.001) between fluoroscopy and navigation. The biomechanical reconstruction with a residual leg length and global and femoral offset discrepancy less than 5 mm and less than 8 mm, respectively, succeeded in 93% and 98%, respectively, in the navigation group and in 54% and 95%, respectively, in the fluoroscopy group.Intraoperative fluoroscopy and imageless navigation seem equivalent in accuracy and precision to reconstruct leg length and global and femoral offset during MIS THA with the patient in the lateral decubitus position.

Background and Aims: In spite of huge developments in liver surgery during the last decades, morbidity and mortality continue to pose problems in this field. The aim of this study was to identify preoperative predictors for postoperative mortality and morbidity in liver surgery. Material and Methods: In a single-center study, an extensive analysis of a prospective database, including clinical criteria and laboratory tests of patients undergoing liver surgery between July 2007 and July 2012 was performed. Cutoff values of selected laboratory tests were calculated. Results: In all, 337 patients were included in the study. Univariate analysis showed a statistically significant association of preoperative bilirubin, lactate, hemoglobin levels, platelet count, and prothrombin time with postoperative morbidity and mortality. Multivariate analysis revealed preoperatively elevated serum bilirubin and lactate levels as independent predictors for increased postoperative morbidity and mortality after liver surgery. Conclusions: The identified laboratory values showed a statistically significant association with postoperative morbidity and mortality in liver surgery and might be helpful in preoperative patient selection.

Background We recently reported that nocturnal respiratory rate (NRR) predicts non-sudden cardiac death in survivors of myocardial infarction (MI). Here, we present the details of the technique deriving NRR from ECG recordings. Methods Continuous ECG and respiratory chest excursions were simultaneously recorded in 941 MI survivors who were followed-up for 5-years. Mean respiratory rate was derived from the ECG based on RR intervals, QRS amplitudes, and QRS vectors and compared to chest belt measurements. NRR was calculated from Holter-ECGs accordingly using the same ECG processing. Results Directly-measured and ECG-derived respiratory rates were in good agreement. Areas under the ROC curve for 10-min-ECG- and Holter-derived respiratory rate were well in the confidence intervals of that of the chest belt measurement. The optimum dichotomy of NRR for the prediction of mortality was ≥ 18.6 breaths per minute. Conclusions The mean respiratory rate can be precisely derived from continuous ECGs.

Purpose: To establish normal values of the optic nerve sheath diameter (ONSD) in children and adolescents for transbulbar sonography and magnetic resonance imaging. Materials and Methods: In 99 children and adolescents (age: 5.6 – 18.6 years, mean: 12 years) without neurologic or ophthalmologic disease, measurements of the ONSD with transbulbar sonography were performed. For comparison 59 children and adolescents (age: 5.1 – 17.4 years, mean 12.3 years) with a normal MR examination of the brain had measurements of the ONSD on a T2-weighted thin section sequence of the orbit. Besides establishing modality-related normal values, age dependency, accuracy and reproducibility of measurements were assessed. Results: Overall the mean ONSD was 5.75 ± 0.52 mm for transbulbar sonography and 5.69 ± 0.31 mm for MRI. There was no statistical significance between the 95 % percentiles and age for both transbulbar sonography (p = 0.332) and MRI (p = 0.336). As a parameter for the reproducibility of measurements, the repeatability coefficient (RC) was between 0.34 mm and 0.46 mm. The concordance correlation coefficient (CCC) values revealed a high agreement between readers both for transbulbar sonography (0.868) and MRI (0.796). Conclusion: Normal values for ONSD in children and adolescents found in this study are significantly higher than assumed. The values found for transbulbar sonography are confirmed by comparable results for MR measurements. A precise sonographic measurement technique and the consideration of normal values found hereby are essential for correct interpretation of ONSD measurements in children and adolescents.

Liver cirrhosis, myeloproliferative disorders (MPDs) and prothrombotic mutations are aetiologic factors for portal vein thrombosis (PVT). The role and frequency of thrombophilic genetic risk factors in cirrhotic patients is not well established. In this case–control study, we investigated the frequency of Janus kinase 2 (JAK2) (JAK2 V617F), Factor V Leiden (FVL G1691A), and Prothrombin (G20210A) mutations in cirrhotic patients with PVT (LCi+/PVT+ group, n = 21) in comparison with two control collectives (cirrhotic patients without PVT, LCi+/PVT− group, n = 43; PVT patients without liver cirrhosis, LCi−/PVT+ group, n = 29). In the LCi+/PVT+ group, JAK2 V617F was present in 2/21 patients (10 %; p = 0.104 compared to LCi+/PVT−; p = 0.092 compared to LCi−/PVT+), whereas 0/43 LCi+/PVT− patients (0 %; p

Summary Background Knowledge of the bacterial spectrum for acute cholangitis is essential for adequate empiric antibiotic treatment. Aim To analyse the relation of proton pump inhibitors (PPI) with biliary pathogens in patients with acute cholangitis. Methods This retrospective study identified 278 patients with 318 acute cholangitis episodes using an endoscopic database. The relationship between PPI and microbiological outcomes was assessed by logistic and poisson regression analysis for binary and count data. Results In total, 882 pathogens were isolated, of which, 120 cholangitis episodes occurred with PPI; 198 cholangitis episodes without PPI. Multivariate poisson regression analysis showed that PPI use resulted in a 23% increase in the number of biliary pathogens [3.14 vs. 2.55 (Δ = 0.59), P

Background Radial artery applanation tonometry technology can be used for continuous non-invasive measurement of arterial pressure (AP). The purpose of this study was to evaluate this AP monitoring technology in intensive care unit (ICU) patients in comparison with invasive AP monitoring using a radial arterial catheter. Methods In 24 ICU patients (German university hospital), AP values were simultaneously recorded on a beat-to-beat basis using radial artery applanation tonometry (T-Line system; Tensys Medical, San Diego, CA, USA) and a radial arterial catheter (contralateral arm). The primary endpoint of the study was to investigate the accuracy and precision of the non-invasively assessed AP measurements with the Bland–Altman method based on averaged 10 beat AP epochs (n=2993 10 beat epochs). Results For mean AP (MAP), systolic AP (SAP), and diastolic AP (DAP), we observed a bias (±standard deviation of the bias; 95% limits of agreement; percentage error) of +2 mm Hg (±6; −11 to +15 mm Hg; 15%), −3 mm Hg (±15; −33 to +27 mm Hg; 23%), and +5 mm Hg (±7; −9 to +19 mm Hg; 22%), respectively. Conclusions In ICU patients, MAP and DAP measurements obtained using radial artery applanation tonometry show clinically acceptable agreement with invasive AP determination with a radial arterial catheter. While the radial artery applanation tonometry technology also allows SAP measurements with high accuracy, its precision for SAP measurements needs to be further improved.

Purpose The aims of our study were to determine first circadian influences on central concentrations of the neuropeptides oxytocin and arginine-vasopressin and second to investigate if these central concentrations are associated with those in the peripheral compartments blood and saliva in neurocritical care patients. We therefore included patients with external ventricular drain who attended a neurosurgical intensive care unit and were not exposed to painful or stressful stimuli during the sampling period. For this purpose, blood, cerebrospinal fluid and saliva were collected in a 24-hour-interval at the timepoints 06:00, 12:00, 18:00 and 24:00. Results In none of the three body fluids examined, significant time-dependent fluctuations of oxytocin and arginine-vasopressin concentrations could be detected during the 24-hour sampling period. The only exception was the subgroup of postmenopausal women whose oxytocin concentrations in cerebrospinal fluid at 12:00 were significantly higher than at 18:00. Correlations of blood and cerebrospinal fluid and blood and saliva neuropeptide levels were very weak to weak at each timepoint. Cerebrospinal fluid and saliva oxytocin levels showed a moderate correlation at 06:00 but did correlate very weak at the other timepoints. Conclusions Central as well as peripheral oxytocin and arginine-vasopressin concentrations in neurocritical care patients did not show significant diurnal fluctuations. No strong correlations between central and peripheral neuropeptide concentrations could be detected under basal conditions. If investigators even though decide to use saliva concentrations as surrogate parameter for central neuropeptide activity, they have to consider that correlations of cerebrospinal fluid and saliva oxytocin seem to be highest in the early morning.

Purpose We compared blood pressure (BP) measurements obtained using radial artery applanation tonometry with invasive BP measurements using a catheter placed in the abdominal aorta through the femoral artery in patients with multiple organ dysfunction syndrome (MODS). Materials and Methods In 23 intensive care unit patients with MODS, we simultaneously assessed BP values for 15 minutes per patient using radial artery applanation tonometry (T-Line TL-200pro device; Tensys Medical Inc, San Diego, Calif) and the arterial catheter (standard-criterion technique). A total of 2879 averaged 10-beat epochs were compared using Bland-Altman plots. Results The mean difference ± SD (with corresponding 95% limits of agreement) between radial artery applanation tonometry–derived BP and invasively assessed BP was +1.0 ± 5.5 mm Hg (−9.9 to +11.8 mm Hg) for mean arterial pressure, −3.3 ± 11.2 mm Hg (−25.3 to +18.6 mm Hg) for systolic arterial pressure, and +4.9 ± 7.0 mm Hg (−8.8 to +18.6 mm Hg) for diastolic arterial pressure, respectively. Conclusions In intensive care unit patients with MODS, mean arterial pressure and diastolic arterial pressure can be determined accurately and precisely using radial artery applanation tonometry compared with central aortic values obtained using a catheter placed in the abdominal aorta through the femoral artery. Although systolic arterial pressure could also be derived accurately, wider 95% limits of agreement suggest lower precision for determination of systolic arterial pressure.

Background The T-Line TL-200pro (TL-200pro) device (Tensys Medical, Inc., San Diego, CA, USA), based on radial artery tonometry, provides an arterial pressure (AP) waveform and beat-to-beat values of systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP). The aim of the study was to evaluate this non-invasive technique for continuous AP monitoring in medical intensive care unit (ICU) patients. Methods Arterial pressure measurements obtained using the TL-200pro technology were compared using Bland–Altman analysis with values measured directly from a femoral arterial catheter in 34 ICU patients. Results Arterial pressure values were analysed and compared in 4502 averaged 10-beat epochs. A bias of +0.72 mm Hg (95% limits of agreement −9.37 to +10.82 mm Hg) was observed for MAP. For SAP and DAP, there was a mean difference of −1.39 mm Hg (95% limits of agreement −18.74 to +15.96 mm Hg) and +4.36 mm Hg (95% limits of agreement −8.66 to +17.38 mm Hg), respectively. The percentage error for MAP, SAP, and DAP was 12%, 14%, and 21%, respectively. Conclusions Arterial pressure measurement based on radial artery tonometry using the TL-200pro technology is feasible in medical ICU patients. The TL-200pro system is capable of providing MAP values with high accuracy (low mean difference) and precision (narrow limits of agreement) compared with MAP measured invasively using a femoral arterial catheter. The TL-200pro technology is promising for the measurement of SAP and DAP but further development is necessary to improve accuracy and precision.

Background The Mosaic bioprosthesis (Medtronic Inc., Minneapolis, Minnesota, United States), a stented porcine aortic valve, combines glutaraldehyde fixation with zero-pressure, root-pressure techniques and antimineralization treatment with amino-oleic acid for improved hemodynamics and tissue durability. The first device has been implanted worldwide at the authors' institution in September 1993. The aim of the present study was to collect mid- to long-term data of the prosthesis. Materials and Methods A total of 272 patients (124 males and 148 females) underwent isolated aortic valve replacement with the Mosaic bioprosthesis between September 1993 and August 2007. Median age at implant was 76.8 years (range, 31.3 to 90.7). Median follow-up was 12.0 years (range, 0 to 17.2 years); follow-up was complete for 223 (82%) patients. Results Early mortality (30 days) was 4% (12 patients). Overall survival at 5, 10, 15, and 17 years was 68.6% ± 3.1%, 36.4% ± 3.3%, 17.1% ± 3.6%, and 10.7% ± 4.3%, respectively. Eleven late deaths (5%) were cardiac related. There were 24 thromboembolic events, 1 hemorrhagic, and 6 reoperations/explants. At a median follow-up of 12 years, freedom from any cause of death was 27.0% ± 3.2% acting as a competing risk for the incidence of thromboembolic events (16.4% ± 3.5%), hemorrhage (0.5% ± 0.5%), and reoperation/explant (4.1% ± 1.8%). Two redos were due to structural valve deterioration (SVD), two for nonstructural dysfunction (paravalvular leakage), one for thrombosed prosthesis, and one for endocarditis. Conclusions Performance and late outcome of the Mosaic bioprosthesis was satisfactory during 17 years after clinical introduction. The Mosaic bioprosthesis showed low incidence of SVD or need for reoperation in the long term.

Esophagectomy is a challenging operation with considerable potential for postoperative complications, including chylothorax. Because no randomized controlled trial or metaanalysis is available to clarify the incidence of chylothorax in esophageal cancer surgery, the authors analyzed their own institutional data for 1,856 patients and performed a systematic review using the MEDLINE database (9,794 patients) to identify risk factors, compare success rates of therapeutic approaches, and investigate long-term outcomes. The overall institutional chylothorax rate was 2 % (n = 39). Reoperation was performed for 69 % of the patients. No significant difference was noted between the transthoracic and transhiatal approaches. Regression analysis showed neoadjuvant treatment (odds ratio [OR], 0.302; p = 0.001) and tumor type (OR, 0.304; p = 0.002) to be independent risk factors. The systematic review included 12 studies. Chylothorax occurred for 2.6 % of the patients. Treatment favored reoperation in five studies (70–100 %) and a conservative approach in four studies (58–72 %), with equal mortality rates. No significant difference was found between the transthoracic and transhiatal approaches. Chylothorax rates are low in high-volume centers (2–3 %). No significant difference was noted between the transthoracic and transhiatal approaches. Neoadjuvant treatment and tumor type were shown to be independent risk factors. Treatment concept (reoperation vs conservative treatment) did not affect long-term survival.

Summary Background Perioperative acquired factor XIII deficiency has been looked upon as a potential cause of postoperative bleeding in adult cardiac surgery. Methods Forty-four infants were prospectively studied for the time course of factor XIII in plasma and the effect on chest tube drainage (CTD) and transfusion requirements in the first 24 h after surgery. A reconstituted blood prime (RBP) with fresh–frozen plasma (FFP) and packed red blood cells (PRBC) was used. Samples were taken at baseline, after cardiopulmonary bypass and upon arrival in the ICU. Differences in blood loss and transfusion requirements based on a cutoff value of 70% factor XIII activity at the time of ICU admission were also calculated. Results Baseline factor XIII activity was 79%, decreased to 71% after CPB (P = 0.102) and increased back up to 77% at ICU arrival (P = 0.708). There was no significant correlation between factor XIII, CTD, age, cyanosis, platelet count, and transfusion requirements at any time point. Only preoperative fibrinogen levels correlated significantly with factor XIII activity. Perioperative blood transfusions (PRBC P = 0.712, FFP P = 0.909, platelets P = 0.807) and chest tube losses (P = 0.424 at 6 h and P = 0.215 at 24 h) were not significantly different above or below a 70% factor XIII activity at ICU arrival. Conclusion Factor XIII activity in infants with congenital heart defects is within the lower range of normal adults, independent of patient's age and the presence of cyanosis. Reconstituted blood prime maintains factor XIII activity at sufficient levels during pediatric cardiac surgery. We could not detect a correlation between FXIII and CTD.