Architecture of the outbred brown fat proteome defines regulators of metabolic physiology.

Brown adipose tissue (BAT) regulates metabolic physiology. However, nearly all mechanistic studies of BAT protein function occur in a single inbred mouse strain, which has limited the understanding of generalizable mechanisms of BAT regulation over physiology. Here, we perform deep quantitative proteomics of BAT across a cohort of 163 genetically defined diversity outbred mice, a model that parallels the genetic and phenotypic variation found in humans. We leverage this diversity to define the functional architecture of the outbred BAT proteome, comprising 10,479 proteins. We assign co-operative functions to 2,578 proteins, enabling systematic discovery of regulators of BAT. We also identify 638 proteins that correlate with protection from, or sensitivity to, at least one parameter of metabolic disease. We use these findings to uncover SFXN5, LETMD1, and ATP1A2 as modulators of BAT thermogenesis or adiposity, and provide OPABAT as a resource for understanding the conserved mechanisms of BAT regulation over metabolic physiology.

Mechanical power made simple: validating a simplified calculation of mechanical power in preterm lungs.

BACKGROUND: The incidence of chronic lung disease is increasing, suggesting a need to explore novel ways to understand ventilator induced lung injury (VILI) in preterm infants. Mechanical power (MP) is a unifying measure of energy transferred to the respiratory system and a proposed determinant of VILI. The gold-standard method for calculating MP (geometric method) is not feasible in the clinical setting. This has prompted the derivation of simplified equations for calculating MP. OBJECTIVE: To validate the agreement between a simplified calculation of MP (MPSimple) and the true MP calculated using the geometric method (MPRef). METHODS: MPSimple and MPRef was calculated in mechanically ventilated preterm lambs (n = 71) and the agreement between both measures was determined using intraclass correlation coefficients (ICC), linear regression, and Bland-Altman analysis. RESULTS: A strong linear relationship (adjusted R2 = 0.98), and excellent agreement (ICC = 0.99, 95% CI = 0.98-0.99) between MPSimple and MPRef was demonstrated. Bland-Altman analysis demonstrated a negligible positive bias (mean difference = 0.131 J/min·kg). The 95% limits of agreement were -0.06 to 0.32 J/min·kg. CONCLUSIONS: In a controlled setting, there was excellent agreement between MPSimple and gold-standard calculations. MPSimple should be validated and explored in preterm neonates to assess the cause-effect relationship with VILI and neonatal outcomes. IMPACT STATEMENT: Mechanical power (MP) unifies the individual components of ventilator induced lung injury (VILI) and provides an estimate of total energy transferred to the respiratory system during mechanical ventilation. As gold-standard calculations of mechanical power at the bedside are not feasible, alternative simplified equations have been proposed. In this study, MP calculated using a simplified equation had excellent agreement with true MP in mechanically ventilated preterm lambs. These results lay foundations to explore the role of MP in neonatal VILI and determine its relationship with short and long term respiratory outcomes.

Setting positive end-expiratory pressure by using electrical impedance tomography.

PURPOSE OF REVIEW: This review presents the principles and possibilities of setting positive end-expiratory pressure (PEEP) using electrical impedance tomography (EIT). It summarizes the major findings of recent studies where EIT was applied to monitor the effects of PEEP on regional lung function and to guide the selection of individualized PEEP setting. RECENT FINDINGS: The most frequent approach of utilizing EIT for the assessment of PEEP effects and the PEEP setting during the time period from January 2022 till June 2023 was based on the analysis of pixel tidal impedance variation, typically acquired during stepwise incremental and/or decremental PEEP variation. The most common EIT parameters were the fraction of ventilation in various regions of interest, global inhomogeneity index, center of ventilation, silent spaces, and regional compliance of the respiratory system. The studies focused mainly on the spatial and less on the temporal distribution of ventilation. Contrast-enhanced EIT was applied in a few studies for the estimation of ventilation/perfusion matching. SUMMARY: The availability of commercial EIT devices resulted in an increase in clinical studies using this bedside imaging technology in neonatal, pediatric and adult critically ill patients. The clinical interest in EIT became evident but the potential of this method in clinical decision-making still needs to be fully exploited.

The Evolving Role of Dendritic Cells in Atherosclerosis.

Atherosclerosis, a major contributor to cardiovascular morbidity and mortality, is characterized by chronic inflammation of the arterial wall. This inflammatory process is initiated and maintained by both innate and adaptive immunity. Dendritic cells (DCs), which are antigen-presenting cells, play a crucial role in the development of atherosclerosis and consist of various subtypes with distinct functional abilities. Following the recognition and binding of antigens, DCs become potent activators of cellular responses, bridging the innate and adaptive immune systems. The modulation of specific DC subpopulations can have either pro-atherogenic or atheroprotective effects, highlighting the dual pro-inflammatory or tolerogenic roles of DCs. In this work, we provide a comprehensive overview of the evolving roles of DCs and their subtypes in the promotion or limitation of atherosclerosis development. Additionally, we explore antigen pulsing and pharmacological approaches to modulate the function of DCs in the context of atherosclerosis.

Brown adipose tissue is not associated with cachexia or increased mortality in a retrospective study of patients with cancer.

Although brown fat is strongly associated with a constellation of cardiometabolic benefits in animal models and humans, it has also been tied to cancer cachexia. In humans, cancer-associated cachexia increases mortality, raising the possibility that brown fat in this context may be associated with increased cancer death. However, the effect of brown fat on cancer-associated cachexia and survival in humans remains unclear. Here, we retrospectively identify patients with and without brown fat on fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) scans obtained as part of routine cancer care and assemble a cohort to address these questions. We did not find an association between brown fat status and cachexia. Furthermore, we did not observe an association between brown fat and increased mortality in patients with cachexia. Our analyses controlled for confounding factors including age at cancer diagnosis, sex, body mass index, cancer site, cancer stage, outdoor temperature, comorbid conditions (heart failure, type 2 diabetes mellitus, coronary artery disease, hypertension, dyslipidemia, cerebrovascular disease), and ß-blocker use. Taken together, our results suggest that brown fat is not linked to cancer-associated cachexia and does not worsen overall survival in patients with cachexia.NEW & NOTEWORTHY This study finds that brown fat is not linked to cancer-associated cachexia. Moreover, this work shows that brown fat does not worsen overall survival in patients with cachexia.

Three-Dimensional Imaging Provides Detailed Atherosclerotic Plaque Morphology and Reveals Angiogenesis After Carotid Artery Ligation.

RATIONALE: Remodeling of the vessel wall and the formation of vascular networks are dynamic processes that occur during mammalian embryonic development and in adulthood. Plaque development and excessive neointima formation are hallmarks of atherosclerosis and vascular injury. As our understanding of these complex processes evolves, there is a need to develop new imaging techniques to study underlying mechanisms. OBJECTIVE: We used tissue clearing and light-sheet microscopy for 3-dimensional (3D) profiling of the vascular response to carotid artery ligation and induction of atherosclerosis in mouse models. METHODS AND RESULTS: Adipo-Clear and immunolabeling in combination with light-sheet microscopy were applied to image carotid arteries and brachiocephalic arteries, allowing for 3D reconstruction of vessel architecture. Entire 3D neointima formations with different geometries were observed within the carotid artery and scored by volumetric analysis. Additionally, we identified a CD31-positive adventitial plexus after ligation of the carotid artery that evolved and matured over time. We also used this method to characterize plaque extent and composition in the brachiocephalic arteries of ApoE-deficient mice on high-fat diet. The plaques exhibited inter-animal differences in terms of plaque volume, geometry, and ratio of acellular core to plaque volume. A 3D reconstruction of the endothelium overlying the plaque was also generated. CONCLUSIONS: We present a novel approach to characterize vascular remodeling in adult mice using Adipo-Clear in combination with light-sheet microscopy. Our method reconstructs 3D neointima formation after arterial injury and allows for volumetric analysis of remodeling, in addition to revealing angiogenesis and maturation of a plexus surrounding the carotid artery. This method generates complete 3D reconstructions of atherosclerotic plaques and uncovers their volume, geometry, acellular component, surface, and spatial position within the brachiocephalic arteries. Our approach may be used in a number of mouse models of cardiovascular disease to assess vessel geometry and volume. Visual Overview: An online visual overview is available for this article.

Stable patients with suspected myocardial ischemia: comparison of machine-learning computed tomography-based fractional flow reserve and stress perfusion cardiovascular magnetic resonance imaging to detect myocardial ischemia.

BACKGROUND: Machine-Learning Computed Tomography-Based Fractional Flow Reserve (CT-FFRML) is a novel tool for the assessment of hemodynamic relevance of coronary artery stenoses. We examined the diagnostic performance of CT-FFRML compared to stress perfusion cardiovascular magnetic resonance (CMR) and tested if there is an additional value of CT-FFRML over coronary computed tomography angiography (cCTA). METHODS: Our retrospective analysis included 269 vessels in 141 patients (mean age 67 ± 9 years, 78% males) who underwent clinically indicated cCTA and subsequent stress perfusion CMR within a period of 2 months. CT-FFRML values were calculated from standard cCTA. RESULTS: CT-FFRML revealed no hemodynamic significance in 79% of the patients having ≥ 50% stenosis in cCTA. Chi2 values for the statistical relationship between CT-FFRML and stress perfusion CMR was significant (p < 0.0001). CT-FFRML and cCTA (≥ 70% stenosis) provided a per patient sensitivity of 88% (95%CI 64-99%) and 59% (95%CI 33-82%); specificity of 90% (95%CI 84-95%) and 85% (95%CI 78-91%); positive predictive value of 56% (95%CI 42-69%) and 36% (95%CI 24-50%); negative predictive value of 98% (95%CI 94-100%) and 94% (95%CI 90-96%); accuracy of 90% (95%CI 84-94%) and 82% (95%CI 75-88%) when compared to stress perfusion CMR. The accuracy of cCTA (≥ 50% stenosis) was 19% (95%CI 13-27%). The AUCs were 0.89 for CT-FFRML and 0.74 for cCTA (≥ 70% stenosis) and therefore significantly different (p < 0.05). CONCLUSION: CT-FFRML compared to stress perfusion CMR as the reference standard shows high diagnostic power in the identification of patients with hemodynamically significant coronary artery stenosis. This could support the role of cCTA as gatekeeper for further downstream testing and may reduce the number of patients undergoing unnecessary invasive workup.

Recruitable alveolar collapse and overdistension during laparoscopic gynecological surgery and mechanical ventilation: a prospective clinical study.

BACKGROUND: Laparoscopic surgery in Trendelenburg position may impede mechanical ventilation (MV) due to positioning and high intra-abdominal pressure. We sought to identify the positive end-expiratory pressure (PEEP) levels necessary to counteract atelectasis formation ("Open-Lung-PEEP") and to provide an equal balance between overdistension and alveolar collapse ("Best-Compromise-PEEP"). METHODS: In 30 patients undergoing laparoscopic gynecological surgery, relative overdistension and alveolar collapse were assessed with electrical impedance tomography (EIT) during a decremental PEEP trial ranging from 20 to 4 cmH2O in supine position without capnoperitoneum and in Trendelenburg position with capnoperitoneum. RESULTS: In supine position, the median Open-Lung-PEEP was 12 (8-14) cmH2O with 8.7 (4.7-15.5)% of overdistension and 1.7 (0.4-2.2)% of collapse. Best-Compromise-PEEP was 8 (6.5-10) cmH2O with 4.2 (2.4-7.2)% of overdistension and 5.1 (3.9-6.5)% of collapse. In Trendelenburg position with capnoperitoneum, Open-Lung-PEEP was 18 (18-20) cmH 2 O (p < 0.0001 vs supine position) with 1.8 (0.5-3.9)% of overdistension and 0 (0-1.2)% of collapse and Best-Compromise-PEEP was 18 (16-20) cmH2O (p < 0.0001 vs supine position) with 1.5 (0.7-3.0)% of overdistension and 0.2 (0-2.7)% of collapse. Open-Lung-PEEP and Best-Compromise-PEEP were positively correlated with body mass index during MV in supine position but not in Trendelenburg position. CONCLUSION: The PEEP levels required for preventing alveolar collapse and for balancing collapse and overdistension in Trendelenburg position with capnoperitoneum were significantly higher than those required for achieving the same goals in supine position without capnoperitoneum. Even with high PEEP levels, alveolar overdistension was negligible during MV in Trendelenburg position with capnoperitoneum. TRIAL REGISTRATION: This study was prospectively registered at German Clinical Trials registry (DRKS00016974).

Characterization of circulating thrombin in patients with septic shock: a prospective observational study.

Septic shock is characterized by a dysregulated response to infection, hypotension and activation of the coagulation system. Markers of coagulation activation are commonly used to diagnose and monitor ensuing coagulopathies. In this study, we sought to determine levels of circulating thrombin in patients with septic shock. To characterize levels of circulating, active thrombin in patients with septic shock. 48 patients with septic shock were included in this prospective, observational study. Blood samples were obtained on admission, day 1, day 3 and day 6. Levels of active thrombin were measured using a standardized, clinically applicable oligonucleotide (aptamer)-based enzyme-capture assay (OECA). Thrombin levels were correlated with established indirect thrombin parameters, conventional coagulation tests, laboratory parameters, patient characteristics and outcome. Elevated levels of thrombin were detected in 27 patients (56.3%) during the course of the study. Thrombin levels were positively correlated with thrombin-antithrombin complexes (r = 0.30, p < 0.05) and negatively associated with FVII levels (r = - 0.28, p < 0.05). Thrombin levels on admission did not predict 30-day mortality (OR 0.82, 95% CI 0.23-2.92, p = 0.77). Circulating levels of active thrombin can be measured in a subset of patients with septic shock. Although thrombin levels are correlated with established markers of coagulation, they do not provide additional prognostic information.

Noninvasive measurement of stroke volume changes in critically ill patients by means of electrical impedance tomography.

Previous animal experiments have suggested that electrical impedance tomography (EIT) has the ability to noninvasively track changes in cardiac stroke volume (SV). The present study intended to reproduce these findings in patients during a fluid challenge. In a prospective observational study including critically ill patients on mechanical ventilation, SV was estimated via ECG-gated EIT before and after a fluid challenge and compared to transpulmonary thermodilution reference measurements. Relative changes in EIT-derived cardiosynchronous impedance changes in the heart ([Formula: see text]) and lung region ([Formula: see text]) were compared to changes in reference SV by assessing the concordance rate (CR) and Pearson's correlation coefficient (R). We compared 39 measurements of 20 patients. [Formula: see text] did not show to be a reliable estimate for tracking changes of SV (CR = 52.6% and R = 0.13 with P = 0.44). In contrast, [Formula: see text] showed an acceptable trending performance (CR = 94.4% and R = 0.72 with P < 0.0001). Our results indicate that ECG-gated EIT measurements of [Formula: see text] are able to noninvasively monitor changes in SV during a fluid challenge in critically ill patients. However, this was not possible using [Formula: see text]. The present approach is limited by the influences induced by ventilation, posture or changes in electrode-skin contact and requires further validation.

Cardioprotective Effects of Dronedarone Mediated by the Influence on the Expression of Urokinase-Type Plasminogen Activator Receptor.

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.

Adaptive mechanical ventilation with automated minimization of mechanical power-a pilot randomized cross-over study.

BACKGROUND: Adaptive mechanical ventilation automatically adjusts respiratory rate (RR) and tidal volume (VT) to deliver the clinically desired minute ventilation, selecting RR and VT based on Otis' equation on least work of breathing. However, the resulting VT may be relatively high, especially in patients with more compliant lungs. Therefore, a new mode of adaptive ventilation (adaptive ventilation mode 2, AVM2) was developed which automatically minimizes inspiratory power with the aim of ensuring lung-protective combinations of VT and RR. The aim of this study was to investigate whether AVM2 reduces VT, mechanical power, and driving pressure (ΔPstat) and provides similar gas exchange when compared to adaptive mechanical ventilation based on Otis' equation. METHODS: A prospective randomized cross-over study was performed in 20 critically ill patients on controlled mechanical ventilation, including 10 patients with acute respiratory distress syndrome (ARDS). Each patient underwent 1 h of mechanical ventilation with AVM2 and 1 h of adaptive mechanical ventilation according to Otis' equation (adaptive ventilation mode, AVM). At the end of each phase, we collected data on VT, mechanical power, ΔP, PaO2/FiO2 ratio, PaCO2, pH, and hemodynamics. RESULTS: Comparing adaptive mechanical ventilation with AVM2 to the approach based on Otis' equation (AVM), we found a significant reduction in VT both in the whole study population (7.2 ± 0.9 vs. 8.2 ± 0.6 ml/kg, p <  0.0001) and in the subgroup of patients with ARDS (6.6 ± 0.8 ml/kg with AVM2 vs. 7.9 ± 0.5 ml/kg with AVM, p <  0.0001). Similar reductions were observed for ΔPstat (whole study population: 11.5 ± 1.6 cmH2O with AVM2 vs. 12.6 ± 2.5 cmH2O with AVM, p <  0.0001; patients with ARDS: 11.8 ± 1.7 cmH2O with AVM2 and 13.3 ± 2.7 cmH2O with AVM, p = 0.0044) and total mechanical power (16.8 ± 3.9 J/min with AVM2 vs. 18.6 ± 4.6 J/min with AVM, p = 0.0024; ARDS: 15.6 ± 3.2 J/min with AVM2 vs. 17.5 ± 4.1 J/min with AVM, p = 0.0023). There was a small decrease in PaO2/FiO2 (270 ± 98 vs. 291 ± 102 mmHg with AVM, p = 0.03; ARDS: 194 ± 55 vs. 218 ± 61 with AVM, p = 0.008) and no differences in PaCO2, pH, and hemodynamics. CONCLUSIONS: Adaptive mechanical ventilation with automated minimization of inspiratory power may lead to more lung-protective ventilator settings when compared with adaptive mechanical ventilation according to Otis' equation. TRIAL REGISTRATION: The study was registered at the German Clinical Trials Register ( DRKS00013540 ) on December 1, 2017, before including the first patient.

Pentraxin-3 Predicts Short- and Mid-term Mortality in Patients with Sepsis and Septic Shock During Intensive Care Treatment.

BACKGROUND: The prognostic value of the acute phase protein Pentraxin 3 (PTX-3) is not well evaluated in patients with septic shock, which reveal an unacceptably high short- and long-term mortality. New Sepsis-3 definitions are not yet implemented in most biomarker studies. Therefore, this study assesses the prognostic value of PTX-3 for short- and mid-term mortality in patients with sepsis or septic shock, as defined by the latest definitions, treated at a medical intensive care unit (ICU). METHODS: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3, and 8. All-cause mortality was followed up to 30 days and at 6 months. RESULTS: On all three days, PTX-3 levels were able to discriminate non-survivors from survivors at 30 days and 6 months (AUC range: 0.59 - 0.70; 95% CI: 0.52 - 0.79; p ≤ 0.02). Highest PTX-3 levels within the fourth quartiles during the first week of ICU treatment were associated with an increased mortality rate at 30 days (OR = 7; 95% CI: 2.0 - 23.5; p ≤ 0.002) and at 6 months (OR = 5; 95% CI: 2.1 - 11.4; p ≤ 0.006). Additionally, the prognostic value of PTX-3 was proven for all patients as well as in subcohorts of patients with sepsis and septic shock, according to Sepsis-3 criteria, both in univariate and multivariate analyses for 30-day and 6-months all-cause mortality, especially predicting all-cause mortality in septic shock (HRs range: 1.0 - 2.9; 95% CI: 0.3 - 5.1; p ≤ 0.03). CONCLUSIONS: PTX-3 offers prognostic value for the prediction of short- and mid-term all-cause mortality in patients suffering from sepsis and septic shock according to the latest Sepsis-3 criteria.

Determination of respiratory system compliance during pressure support ventilation by small variations of pressure support.

In mechanically ventilated patients, measurement of respiratory system compliance (Crs) is of high clinical interest. Spontaneous breathing activity during pressure support ventilation (PSV) can impede the correct assessment of Crs and also alter the true Crs by inducing lung recruitment. We describe a method for determination of Crs during PSV and assess its accuracy in a study on 20 mechanically ventilated patients. To assess Crs during pressure support ventilation (Crs,PSV), we performed repeated changes in pressure support level by ± 2 cmH2O. Crs,PSV was calculated from the volume change induced by these changes in pressure support level, taking into account the inspiration time and the expiratory time constant. As reference methods, we used Crs, measured during volume controlled ventilation (Crs,VCV). In a post-hoc analysis, we assessed Crs during the last 20% of the volume-controlled inflation (Crs,VCV20). Values were compared by linear regression and Bland-Altman methods comparison. Comparing Crs,PSV to the reference value Crs,VCV, we found a coefficient of determination (r2) of 0.90, but a relatively high bias of - 7 ml/cm H2O (95% limits of agreement - 16.7 to + 2.7 ml/cmH2O). Comparison with Crs,VCV20 resulted in a negligible bias (- 1.3 ml/cmH2O, 95% limits of agreement - 13.9 to + 11.3) and r2 of 0.81. We conclude that the novel method provides an estimate of end-inspiratory Crs during PSV. Despite its limited accuracy, it might be useful for non-invasive monitoring of Crs in patients undergoing pressure support ventilation.

Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

BACKGROUND: Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). METHODS: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. RESULTS: PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). CONCLUSION: PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. TRIAL REGISTRATION: NCT01535534 . Registered 14.02.2012.

Follow-up of iatrogenic aorto-coronary "Dunning" dissections by cardiac computed tomography imaging.

BACKGROUND: Iatrogenic aorto-coronary dissections following percutaneous coronary interventions (PCI) represent a rare but potentially life threatening complication. This restrospective and observational study aims to describe our in-house experience for timely diagnostics and therapy including cardiovascular imaging to follow-up securely high-risk patients with Dunning dissections. METHODS: Dunning dissections (DD) occurred during clinical routine PCIs, which were indicated according to current ESC guidelines. Diagnostic assessment, treatment and follow-up were based on coronary angiography with PCI or conservative treatment and cardiac computed tomography (cCTA) imaging. RESULTS: A total of eight patients with iatrogenic DD were included. Median age was 69 years (IQR 65.8-74.5). Patients revealed a coronary multi-vessel-disease in 75% with a median SYNTAX-II-score of 35.3 (IQR 30.2-41.2). The most common type of DD was type III (50%), followed by type I (38%) and type II (13%). In most patients (88%) the DD involved the right coronary arterial ostium. 63% were treated by PCI, the remaining patients were treated conservatively. 88% of patients received at least one cCTA within 2 days, 50% were additionally followed-up by cCTA within a median of 6 months (range: 4-8 months) without any residual. CONCLUSION: Independently of the type of DD (I-III) it was demonstrated that cCTA represents a valuable imaging modality for detection and follow-up of patients with DDs.

Liver and cholestatic parameters as prognostic biomarkers of in-hospital MACE in patients with STEMI.

BACKGROUND: Liver and cholestatic parameters are increased in ST-segment elevation myocardial infarction (STEMI). The aim of the present study was to evaluate the prognostic value of these parameters to predict in-hospital major adverse cardiac events (MACE) in patients after STEMI. MATERIALS AND METHODS: Blood samples of patients with STEMI, who underwent percutaneous coronary intervention (PCI) and stent implantation, were retrospectively analysed and correlated with in-hospital events. RESULTS: The study population consisted of 847 consecutive patients (62·4 ± 13·43 years; 73·8% male). The total in-hospital MACE rate was 9·8%, driven by death of any cause (8·4%). The Mann-Whitney U-test revealed that liver and cholestatic parameters (alanine transaminase P < 0·0001, aspartate transaminase P < 0·0001, alkaline phosphatase (AP) P < 0·0001, gamma-glutamyl transferase P = 0·0006 and total bilirubin P = 0·0023) were significantly higher in the MACE group. Further logistic regression analyses confirmed the correlation between MACE and all five laboratory markers, even after adjustment for age and heart enzymes. Logistic regression model revealed AP to be the best predictor for worth outcome (OR 1·0188; 95% CI 1·0118-1·0258; P < 0·0001). CONCLUSION: Liver and cholestatic parameters are elevated in patients after STEMI. Increased AP is associated with in-hospital event rates.