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Cardiovascular magnetic resonance (CMR) has favorable characteristics for diagnostic evaluation and risk stratification of patients with known or suspected CAD. CMR utilization in CAD detection is growing fast. However, data on its cost-effectiveness are scarce. The goal of this study is to compare the costs of two strategies for detection of significant coronary artery stenoses in patients with suspected coronary artery disease (CAD): 1) Performing CMR first to assess myocardial ischemia and/or infarct scar before referring positive patients (defined as presence of ischemia and/or infarct scar to coronary angiography (CXA) versus 2) a hypothetical CXA performed in all patients as a single test to detect CAD. A subgroup of the European CMR pilot registry was used including 2,717 consecutive patients who underwent stress-CMR. From these patients, 21% were positive for CAD (ischemia and/or infarct scar), 73% negative, and 6% uncertain and underwent additional testing. The diagnostic costs were evaluated using invoicing costs of each test performed. Costs analysis was performed from a health care payer perspective in German, United Kingdom, Swiss, and United States health care settings. In the public sectors of the German, United Kingdom, and Swiss health care systems, cost savings from the CMR-driven strategy were 50%, 25% and 23%, respectively, versus outpatient CXA. If CXA was carried out as an inpatient procedure, cost savings were 46%, 50% and 48%, respectively. In the United States context, cost savings were 51% when compared with inpatient CXA, but higher for CMR by 8% versus outpatient CXA. This analysis suggests that from an economic perspective, the use of CMR should be encouraged as a management option for patients with suspected CAD.

Background Preoperative devascularization might improve local control and thus the outcome of patients with soft tissue sarcoma (STS). The multikinase inhibitor pazopanib has antiangiogenic effects and is approved for treating metastatic STS. We conducted a trial of preoperative pazopanib therapy in high-risk STS. Methods This single-arm, phase II trial included patients with resectable, non-metastatic, treatment-naïve, high-risk STS. Patients received pazopanib 800 mg daily while waiting for surgery (21-day ‘window of opportunity’). The primary endpoint was metabolic response rate (MRR; proportion of patients with ≥ 50% reduction of mean standardized uptake value [SUV mean ] in post- vs. pretreatment fluorodeoxyglucose–positron emission tomography/computed tomography [FDG-PET-CT]). Planned sample size was 35 patients (type I error, 5%; type II error, 20%). A translational substudy explored associations between response and concentration of circulating angiogenic factors. Results Futility analysis was performed after 21 patients (11 female, mean age 67 years; liposarcoma n   =  15); 17/21 patients were evaluable for the primary endpoint. The MRR was 1/17 (5.9%, 95% confidence interval < 0.01–0.29). Mean change in SUV mean of post- versus pretreatment PET was a 6% decrease (range 65% decrease to 34% increase); 7/21 (33.3%) patients had 12 grade 3/4 toxicities, and 19/21 (95.2%) patients were resected (all R0). One (4.8%) patient suffered a grade 4 postoperative complication (anastomotic leakage). Circulating endothelial progenitor cells, soluble vascular endothelial growth factor, and angiopoietin-2 concentrations showed no relevant changes during treatment. Conclusions Although this study showed that preoperative pazopanib is not effective for unselected high-risk STS patients, relevant treatment effects were observed in a single patient. Future research needs to better define subgroups potentially benefiting from preoperative pazopanib treatment. ClinicalTrials.gov identifier NCT01543802.

Anemia has been shown to be a risk factor for coronary artery disease (CAD) and mortality, whereas the role of iron metabolism remains controversial. We analyzed iron metabolism and its associations with cardiovascular death and total mortality in patients undergoing coronary angiography with a median follow-up of 9.9 years. Hemoglobin and iron status were determined in 1480 patients with stable CAD and in 682 individuals in whom significant CAD had been excluded by angiography. Multivariate-adjusted hazard ratios (HRs) for total mortality in the lowest quartiles of iron, transferrin saturation, ferritin, soluble transferrin receptor (sTfR), and hemoglobin were 1.22 (95% CI, 0.96-1.60), 1.23 (95% CI, 0.97-1.56), 1.27 (95% CI, 1.02-1.58), 1.26 (95% CI, 0.97-1.65), and 0.99 (95% CI, 0.79-1.24), respectively, compared to the second or third quartile, which served as reference (1.00) because of a J-shaped association. The corresponding HRs for total mortality in the highest quartiles were 1.44 (95% CI, 1.10-1.87), 1.37 (95% CI, 1.05-1.77), 1.17 (95% CI, 0.92-1.50), 1.76 (95% CI, 1.39-2.22), and 0.83 (95% CI, 0.63-1.09). HRs for cardiovascular death were similar. For hepcidin, the adjusted HRs for total mortality and cardiovascular deaths were 0.62 (95% CI, 0.49-0.78) and 0.70 (95% CI, 0.52-0.90) in the highest quartile compared to the lowest one. In stable patients undergoing angiography, serum iron, transferrin saturation, sTfR, and ferritin had J-shaped associations and hemoglobin only a marginal association with cardiovascular and total mortality. Hepcidin was continuously and inversely related to mortality.

Cardiovascular risk assessment in patients with diabetes relies on traditional risk factors. However, numerous novel biomarkers have been found to be independent predictors of cardiovascular disease, which might significantly improve risk prediction in diabetic patients. We aimed to improve prediction of cardiovascular risk in diabetic patients by investigating 135 evolving biomarkers. Based on selected biomarkers a clinically applicable prediction algorithm for long-term cardiovascular mortality was designed. We prospectively enrolled 864 diabetic patients of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study with a median follow-up of 9.6 years. Independent risk factors were selected using bootstrapping based on a Cox regression analysis. The following seven variables were selected for the final multivariate model: NT-proBNP, age, male sex, renin, diabetes duration, Lp-PLA2 and 25-OH vitamin D3. The risk score based on the aforementioned variables demonstrated an excellent discriminatory power for 10-year cardiovascular survival with a C-statistic of 0.76 (P < 0.001), which was significantly better than the established UKPDS risk engine (C-statistic = 0.64, P < 0.001). Net reclassification confirmed a significant improvement of individual risk prediction by 22% (95% confidence interval: 14–30%) compared to the UKPDS risk engine (P < 0.001). The VILDIA score based on traditional cardiovascular risk factors and reinforced with novel biomarkers outperforms previous risk algorithms.

Nosocomial infections are a common complication in clinical practice with major impact on surgical success and patient outcome. The probability of nosocomial infections is rapidly increasing during hospitalization. Therefore, we investigated the impact of a prolonged pre-operative hospital stay on the development of post-operative infection. Within this prospective observational study, 200 patients scheduled for elective cardiac surgery were enrolled. Patients were followed during hospital admission and screened for the development of nosocomial infection. Logistic regression analysis was used to assess the impact of a prolonged pre-operative hospital stay on the development of infection. A total of 195 patients were suitable for the final analysis. We found a strong and direct association of the duration of pre-operative hospital stay and the number of patients developing infection (+23.5%; p = 0.006). Additionally, the length of patients’ pre-operative hospital stay was independently associated with the development of post-operative nosocomial infection, with an adjusted OR per day of 1.38 (95%CI: 1.02–1.86; p = 0.036). A prolonged pre-operative hospital stay was significantly associated with the development of nosocomial infection after cardiac surgery. Those findings need to be considered in future clinical patient management in order to prevent unnecessary antibiotic use and potential harm to patients.

BackgroundHeterozygous mutations in the CASK gene in Xp11.4 have been shown to be associated with a distinct brain malformation phenotype in females, including disproportionate pontine and cerebellar hypoplasia.MethodsThe study characterised the CASK alteration in 20 new female patients by molecular karyotyping, fluorescence in situ hybridisation, sequencing, reverse transcriptase (RT) and/or quantitative real-time PCR. Clinical and brain imaging data of a total of 25 patients were reviewed.Results11 submicroscopic copy number alterations, including nine deletions of ∼11 kb to 4.5 Mb and two duplications, all covering (part of) CASK, four splice, four nonsense, and one 1 bp deletion are reported. These heterozygous CASK mutations most likely lead to a null allele. Brain imaging consistently showed diffuse brainstem and cerebellar hypoplasia with a dilated fourth ventricle, but of remarkably varying degrees. Analysis of 20 patients in this study, and five previously reported patients, revealed a core clinical phenotype comprising severe developmental delay/intellectual disability, severe postnatal microcephaly, often associated with growth retardation, (axial) hypotonia with or without hypertonia of extremities, optic nerve hypoplasia, and/or other eye abnormalities. A recognisable facial phenotype emerged, including prominent and broad nasal bridge and tip, small or short nose, long philtrum, small chin, and/or large ears.ConclusionsThese findings define the phenotypic spectrum associated with CASK loss-of-function mutations. The combination of developmental and brain imaging features together with mild facial dysmorphism is highly suggestive of this disorder and should prompt subsequent testing of the CASK gene.

In this study data and results of a high-resolution experiment in Cephalonia (Greece) regarding empirical basin effects are presented. A total of 59 velocimeters and 17 accelerometers were deployed in the basin of Argostoli Cephalonia (Greece), for a period of 7 months (September 2011–April 2012). Due to high seismicity of the western Greece and surrounding area this array recorded thousands of local, regional and global events. Data used in this work come from a selection of 162 regional and local earthquakes, 3 km ≤ R ≤ 600 km, with magnitude range, 1.0 ≤ M ≤ 5.2. Based on high signal-to-noise ratio recordings and two selected reference stations, variation of several intensity measures (PGA, PGV, Arias Intensity, Cumulative Absolute Velocity), significant duration, HVSR and SSR of ground motion recordings on soil sites within the basin is carefully examined for a range of frequencies of engineering interest.Comparison of results with a detailed 2D geologic model shows a good consistency both in amplification and frequency domain. Influence of “reference” site on ground motion variation of soil sites is also discussed in light of our results. Finally, it is suggested that 2D or/and 3D theoretical modeling should be performed given the availability of geological and geophysical parameters to define a realistic model of the basin. Results of this study can undoubtedly serve in model validation and improvement of ground motion simulation tools.

Post-operative atrial fibrillation (POAF) is postulated as a complex interaction of different pathogenic factors, suggesting inflammatory processes as a main trigger of this particular type of atrial fibrillation. Therefore, the study sought to assess the impact of cellular immunity on the development of POAF. Comparing patients developing POAF to individuals free of POAF the fraction of CD4 + CD28 null T Lymphocytes was significantly higher in individuals developing POAF (11.1% [POAF] vs. 1.9% [non-POAF]; p < 0.001). CD4 + CD28 null cells were independently associated with the development of POAF with an adjusted odds ratio per one standard deviation of 4.89 (95% CI: 2.68–8.97; p < 0.001). Compared to N-terminal Pro-Brain Natriuretic Peptide, the fraction of CD4 + CD28 null cells demonstrated an increased discriminatory power for the development of POAF (NRI: 87.9%, p < 0.001; IDI: 30.9%, p < 0.001). Interestingly, a pre-operative statin-therapy was associated with a lower fraction of CD4 + CD28 null cells (p < 0.001) and showed an inverse association with POAF (p < 0.001). CD4 + CD28 null cells proved to be predictive for the development of POAF after cardiac surgery. Our results potentially indicate an auto-immune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF, which might be modified via the anti-inflammatory potential of a pre-operative statin-therapy.

With the Arctic rapidly changing, the needs to observe, understand, and model the changes are essential. To support these needs, an annual cycle of observations of atmospheric properties, processes, and interactions were made while drifting with the sea ice across the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition from October 2019 to September 2020. An international team designed and implemented the comprehensive program to document and characterize all aspects of the Arctic atmospheric system in unprecedented detail, using a variety of approaches, and across multiple scales. These measurements were coordinated with other observational teams to explore crosscutting and coupled interactions with the Arctic Ocean, sea ice, and ecosystem through a variety of physical and biogeochemical processes. This overview outlines the breadth and complexity of the atmospheric research program, which was organized into 4 subgroups: atmospheric state, clouds and precipitation, gases and aerosols, and energy budgets. Atmospheric variability over the annual cycle revealed important influences from a persistent large-scale winter circulation pattern, leading to some storms with pressure and winds that were outside the interquartile range of past conditions suggested by long-term reanalysis. Similarly, the MOSAiC location was warmer and wetter in summer than the reanalysis climatology, in part due to its close proximity to the sea ice edge.The comprehensiveness of the observational program for characterizing and analyzing atmospheric phenomena is demonstrated via a winter case study examining air mass transitions and a summer case study examining vertical atmospheric evolution. Overall, the MOSAiC atmospheric program successfully met its objectives and was the most comprehensive atmospheric measurement program to date conducted over the Arctic sea ice.The obtained data will support a broad range of coupled-system scientific research and provide an important foundation for advancing multiscale modeling capabilities in the Arctic.