Computed tomography pulmonary angiography (CT-PA) is frequently used in the diagnostic workup of pulmonary embolism (PE), even in highly radiosensitive patient populations. This study aims to assess ...CT-PA with reduced z -axis coverage (compared with a standard scan range covering the entire lung) for its sensitivity for detecting PE and its potential to reduce the radiation dose.
We retrospectively analyzed 602 consecutive CT-PA scans with definite or possible PE reported. A reduced scan range was defined based on the topogram, where the cranial slice was set at the top of the aortic arch and the caudal slice at the top of the lower hemidiaphragm. Locations of emboli in relation to the reduced scan range were recorded.
We included 513 CT-PA scans with definite acute PE in statistical analysis. Patients' median age was 66 (52 to 77) years, 46% were female. Median dose length product was 270.8 (111.3 to 503.9) mGy*cm. Comparing the original and reduced scan ranges, the mean scan length was significantly reduced by 48.0±8.6% (26.8±3.0 vs. 13.9±2.6 cm, P <0.001). Single emboli outside the reduced range in addition to emboli within were found in 15 scans (2.9%), while only 1 scan (0.2%) had an embolus outside the reduced range and none within it. The resulting sensitivity of CT-PA with reduced scan range was 99.81% (95% confidence interval: 98.74%-99.99%) for detecting any PE.
A reduced scan length in CT-PA, as defined above, would substantially decrease radiation dose while maintaining diagnostic accuracy for detecting PE.
•The adsorption of cationic starches onto cellulose was investigated in real-time.•All cationic starches adsorbed irreversibly onto cellulose thin films.•The adsorption behavior was linked to ...intrinsic properties of the cationic starches.
Industrially relevant, commercially available cationic starches have been investigated towards their interaction capacity with cellulose thin films derived from trimethylsilyl cellulose (TMSC). The starches used in this study stem from different sources (potato, pea, corn) and featured rather low degrees of substitution ranging from 0.030 to 0.062. The interaction of those starches with cellulose thin films was studied by surface plasmon resonance spectroscopy under flow conditions using concentrations of 1.0mgml−1 and a flow rate of 25μlmin−1. All the investigated starches employed in this study were capable to efficiently interact with the slightly negatively charged cellulose surface leading to irreversible deposition on the surface. As complementary techniques atomic force microscopy and x-ray photoelectron spectroscopy were used to confirm the presence of the starches on the cellulose film surface. Further, dynamic light scattering and size exclusion chromatography measurements were performed to correlate adsorbed amount, particle size and molecular weight of the starches to their interaction behavior.
Atezolizumab/bevacizumab (atezo/bev) and lenvatinib have demonstrated efficacy as first-line therapies for hepatocellular carcinoma (HCC). However, vascular endothelial growth factor (VEGF) ...inhibition with these therapies may be associated with the risk of bleeding and thromboembolic events. In this study, we evaluated the efficacy and safety with focus on the bleeding and thromboembolic events of atezo/bev vs. lenvatinib in a large, multicenter real-world population.
This study is based on HCC cohorts from seven centers in Germany and Austria. Incidences of bleeding or thromboembolic events and efficacy outcomes were assessed and compared.
In total, 464 patients treated with atezo/bev (n = 325) or lenvatinib (n = 139) were analyzed. Both groups were balanced with respect to demographics, presence of liver cirrhosis, and variceal status. Duration of therapy did not differ between groups. Within 3 months of therapy, bleeding episodes were described in 57 (18%) patients receiving atezo/bev compared with 15 (11%) patients receiving lenvatinib (p = 0.07). Variceal hemorrhage occurred in 11 (3%) patients treated with atezo/bev compared with 4 (3%) patients treated with lenvatinib (p = 0.99). Thromboembolic events were reported in 19 (6%) of patients in the atezo/bev cohort compared with 5 (4%) patients in the lenvatinib cohort (p = 0.37). In addition, incidence of overall bleeding, variceal hemorrhage, and thromboembolic events did not differ significantly in patients who received either atezo/bev or lenvantinib for 6 months.
Safety considerations related to bleeding and thromboembolic events may not be helpful in guiding clinical decision-making when choosing between atezo/bev and lenvatinib.
The inhibition of VEGF by current first-line therapies for HCC, such as atezolizumab/bevacizumab or lenvatinib, may be associated with the risk of bleeding and thromboembolic events. Studies comparing the incidence of these side effects between atezolizumab/bevacizumab and lenvatinib, which are preferred treatments over sorafenib for HCC, are needed. Differences in this side effect profile may influence the choice of first-line therapy by treating physicians. Because no significant differences were observed regarding bleeding or thromboembolic events between both therapies in the present study, we conclude that safety considerations related to these events may not be helpful in guiding clinical decision-making when choosing between atezolizumab/bevacizumab and lenvatinib.
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•Evaluation of the efficacy and safety of atezolizumab/bevacizumab and lenvatinib in a large real-world population of 464 patients with HCC.•Compared with lenvatinib, atezolizumab/bevacizumab improves ORR.•No significant differences in bleeding or thromboembolic events were observed.•In atezolizumab/bevacizumab-treated patients, spleen size and history of variceal bleeding were associated with GI-bleeding risk, while anticoagulation was associated with non-GI bleeding risk.
Bilateral inferior petrosal sinus sampling (BIPSS) is regarded as gold standard to differentiate between Cushing´s disease (CD) and ectopic Cushing's syndrome (ECS). However, published data e.g. on ...the diagnostic value of additional prolactin analysis is controversial. Thus, we evaluated the diagnostic performance of BIPSS with and without prolactin in a multicenter study.
Retrospective study in 5 European reference centers. Patients with overt adrenocorticotropin (ACTH)-dependent Cushing's syndrome at the time of BIPSS with human corticotropin-releasing hormone stimulation were eligible. Cut-offs for the inferior petrosal sinus (IPS) to peripheral (P) ACTH ratio and the normalized ACTH:prolactin IPS:P ratio were calculated via receiver operator characteristics analyses (reference: CD).
156 patients with BIPSS were identified. Of these, 120 patients (92 (77%) females; 106 (88%) CD, 14 (12%) ECS) had either histopathologically confirmed tumors or biochemical remission and/or adrenal insufficiency after surgery; only this subgroup was analyzed by ROC analysis. The optimal cut-offs for the ACTH IPS:P ratio were ≥1.9 at baseline (sensitivity 82.1% (95%CI 73.2-88.6), specificity 85.7% (95%CI 56.2-97.5), AUC 0.86) and ≥2.1 at 5 minutes post-CRH (sensitivity 91.3% (95%CI 83.6-95.7), specificity 92.9%(95%CI 64.1-99.6), AUC 0.96). A subgroup underwent additional prolactin analysis. An optimal cut-off of ≥1.4 was calculated for the normalized ACTH:prolactin IPS:P ratio (sensitivity 96.0% (95%CI 77.7-99.9), specificity 100% (95%CI 56.1-100), AUC 0.99).
Our study confirms the high accuracy of BIPSS in the differential diagnosis of ACTH-dependent Cushing's syndrome and suggests that the simultaneous measurement of prolactin might further improve the diagnostic performance of this test.
We hypothesized that high-sensitivity cardiac troponin (hs-cTn) and its early change are useful in distinguishing acute myocardial infarction (AMI) from acute cardiac noncoronary artery disease.
In a ...prospective, international multicenter study, hs-cTn was measured with 3 assays (hs-cTnT, Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI Siemens) in a blinded fashion at presentation and serially thereafter in 887 unselected patients with acute chest pain. Accuracy of the combination of presentation values with serial changes was compared against a final diagnosis adjudicated by 2 independent cardiologists. AMI was the adjudicated final diagnosis in 127 patients (15%); cardiac noncoronary artery disease, in 124 (14%). Patients with AMI had higher median presentation values of hs-cTnT (0.113 μg/L interquartile range, 0.049-0.246 μg/L versus 0.012 μg/L interquartile range, 0.006-0.034 μg/L; P<0.001) and higher absolute changes in hs-cTnT in the first hour (0.019 μg/L interquartile range, 0.007-0.067 μg/L versus 0.001 μg/L interquartile range, 0-0.003 μg/L; P<0.001) than patients with cardiac noncoronary artery disease. Similar findings were obtained with the hs-cTnI assays. Adding changes of hs-cTn in the first hour to its presentation value yielded a diagnostic accuracy for AMI as quantified by the area under the receiver-operating characteristics curve of 0.94 for hs-cTnT (0.92 for both hs-cTnI assays). Algorithms using ST-elevation, presentation values, and changes in hs-cTn in the first hour accurately separated patients with AMI and those with cardiac noncoronary artery disease. These findings were confirmed when the final diagnosis was readjudicated with the use of hs-cTnT values and validated in an independent validation cohort.
The combined use of hs-cTn at presentation and its early absolute change excellently discriminates between patients with AMI and those with cardiac noncoronary artery disease.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.
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•Impact of opening eye defects on eye structure in cheese.•Use of computed tomography to characterize food structures.•Eye structure characterization of cheese.•Early detection of eye ...defects in cheese.•Observing the ripening process of cheese with computed tomography.
In Swiss-type cheese the presence of eyes is an important sign of quality. During the ripening process defects in the eye structure can occur. Therefore, monitoring the ripening process is essential.
In this contribution, X-ray micro-computed tomography (CT) was used to investigate open eye defects and the effects of different maturing temperatures on the eye structure in cheese. By varying the ripening conditions, deviations in the eye structure were generated and characterized using a dedicated image post-processing pipeline. Four cheese samples were scanned at a voxel size of (155 μm)3 during defined time periods. By determining the total eye volume, the number of eyes, and the size distribution of the eyes, further information about the course of the ripening process was obtained.
The investigation showed that the duration of pre-maturing and the maturing temperature have influence on the eye formation in semi-hard cheeses. There was a linear increase in total volume during the pre-maturing, but the speed at which the eyes grow seemed to be influenced by other factors e.g. spatial distribution of eyes in the cheese. Furthermore, eyes with a volume <34 mm³ are not all growing during the ripening process. This suggests that not all eyes have the same growth potential.
Three-dimensional data provides additional insights for a better understanding of the formation of eye structure. In addition, CT facilitates the early detection of open eye defects by delivering structural information that can be used to predict the final spatial distribution of eyes in semi-hard cheese.
OBJECTIVE:For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of ...this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival.
DESIGN:Randomized controlled open-label trial.
SETTING:Nine multidisciplinary intensive care units across Denmark.
PATIENTS:A total of 1,200 critically ill patients were included after meeting the following eligibility requirementsexpected intensive care unit stay of ≥24 hrs, nonpregnant, judged to not be harmed by blood sampling, bilirubin <40 mg/dL, and triglycerides <1000 mg/dL (not suspensive).
INTERVENTIONS:Patients were randomized either to the “standard-of-care-only arm,” receiving treatment according to the current international guidelines and blinded to procalcitonin levels, or to the “procalcitonin arm,” in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements.
MEASUREMENTS AND MAIN RESULTS:The primary end point was death from any cause at day 28; this occurred for 31.5% (190 of 604) patients in the procalcitonin arm and for 32.0% (191 of 596) patients in the standard-of-care-only arm (absolute risk reduction, 0.6%; 95% confidence interval CI −4.7% to 5.9%). Length of stay in the intensive care unit was increased by one day (p = .004) in the procalcitonin arm, the rate of mechanical ventilation per day in the intensive care unit increased 4.9% (95% CI, 3.0–6.7%), and the relative risk of days with estimated glomerular filtration rate <60 mL/min/1.73 m was 1.21 (95% CI, 1.15–1.27).
CONCLUSIONS:Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit. The procalcitonin strategy like the one used in this trial cannot be recommended.
Mutations in SCO2 are among the most common causes of COX deficiency, resulting in reduced mitochondrial oxidative ATP production capacity, often leading to hypertrophic cardiomyopathy (HCM). To ...date, none of the recent pertaining reports provide deep understanding of the SCO2 disease pathophysiology. To investigate the cardiac pathology of the disease, we were the first to generate induced pluripotent stem cell (iPSC)‐derived cardiomyocytes (iPSC‐CMs) from SCO2‐mutated patients. For iPSC generation, we reprogrammed skin fibroblasts from two SCO2 patients and healthy controls. The first patient was a compound heterozygote to the common E140K mutation, and the second was homozygote for the less common G193S mutation. iPSC were differentiated into cardiomyocytes through embryoid body (EB) formation. To test the hypothesis that the SCO2 mutation is associated with mitochondrial abnormalities, and intracellular Ca2+‐overload resulting in functional derangements and arrhythmias, we investigated in SCO2‐mutated iPSC‐CMs (compared to control cardiomyocytes): (i) the ultrastructural changes; (ii) the inotropic responsiveness to β‐adrenergic stimulation, increased Ca2+o and angiotensin‐II (AT‐II); and (iii) the Beat Rate Variability (BRV) characteristics. In support of the hypothesis, we found in the mutated iPSC‐CMs major ultrastructural abnormalities and markedly attenuated response to the inotropic interventions and caffeine, as well as delayed afterdepolarizations (DADs) and increased BRV, suggesting impaired SR Ca2+ handling due to attenuated SERCA activity caused by ATP shortage. Our novel results show that iPSC‐CMs are useful for investigating the pathophysiological mechanisms underlying the SCO2 mutation syndrome.
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