Assessment of lesion-associated myocardial ischemia based on fusion coronary CT imaging – the FUSE-HEART study: A protocol for non-randomized clinical trial

Introduction:Multimodality assessment of coronary artery lesions has demonstrated superior effectiveness compared to the conventional approach, for assessing both anatomical and functional significance of a coronary stenosis. Multiple imaging modalities can be integrated into a fusion imaging tool to better assess myocardial ischemia.Material and methods:The FUSE-HEART trial is a single center, prospective, cohort study that will assess the impact of a coronary artery stenosis on myocardial function and viability, based on advanced fusion imaging technics derived from Cardiac Computed Tomography Angiography (CCTA). Moreover, the study will investigate the correlation between morphology and composition of the coronary plaques and myocardial ischemia in the territory irrigated by the same coronary artery. At the same time, imaging parameters will be correlated with inflammatory status of the subjects. The trial will include 100 subjects with coronary lesions found on CCTA examination. The study population will be divided into 2 groups: first group will consist of subjects with anatomically significant coronary lesions on native coronary arteries and the second one will include subjects surviving an acute myocardial infarction. The vulnerability score of the subjects will be calculated based on presence of CCTA vulnerability markers of the coronary plaques: napkin ring sign, positive remodeling, spotty calcifications, necrotic core, and low-density plaques. 3D fusion images of the coronary tree will be generated, integrating the images reflecting wall motion with the ones of coronary circulation. The fusion models will establish the correspondence between plaque composition and wall motion in the subtended myocardium of the coronary artery. The study primary outcome will be represented by the rate of major adverse cardiac events related to myocardial ischemia at 1-year post assessment, in correlation with the degree of coronary artery stenosis and myocardial ischemia or viability.The secondary outcomes are represented by the rate of re-hospitalization, rate of survival and rate of major adverse cardiovascular events (including cardiovascular death or stroke), in correlation with the morphology and composition of atheromatous plaques located in a coronary artery, and myocardial ischemia in the territory irrigated by the same coronary artery.Conclusion:In conclusion, FUSE-HEART will be a study based on modern imaging tools that will investigate the impact of a coronary artery stenosis on myocardial function and viability, using advanced fusion imaging technics derived from CCTA, sighting to validate plaque composition and morphology, together with inflammatory biomarkers, as predictors to myocardial viability.     

Automated clinical trial eligibility prescreening: increasing the efficiency of patient identification for clinical trials in the emergency department

Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials.Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed.Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches.Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials.     

Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-alpha via the PI 3-kinase-Akt signaling pathway

Activation of endothelial nitric oxide synthase (eNOS) in portal hypertensive (PHT) gastric mucosa leads to hyperdynamic circulation and increased susceptibility to injury. However, the signaling mechanisms for eNOS activation in PHT gastric mucosa and the role of TNF-alpha in this signaling remain unknown. In PHT gastric mucosa we studied (1) eNOS phosphorylation (at serine 1177) required for its activation; (2) association of the phosphatidylinositol 3-kinase (PI 3-kinase), and its downstream effector Akt, with eNOS; and, (3) whether TNF-alpha neutralization affects eNOS phosphorylation and PI 3-kinase-Akt activation. To determine human relevance, we used human microvascular endothelial cells to examine directly whether TNF-alpha stimulates eNOS phosphorylation via PI 3-kinase. PHT gastric mucosa has significantly increased (1) eNOS phosphorylation at serine 1177 by 90% (P <.01); (2) membrane translocation (P <.05) and phosphorylation (P <.05) of p85 (regulatory subunit of PI 3-kinase) by 61% and 85%, respectively; (3) phosphorylation (P <.01) and activity (P <.01) of Akt by 40% and 52%, respectively; and (4) binding of Akt to eNOS by as much as 410% (P <.001). Neutralizing anti-TNF-alpha antibody significantly reduced p85 phosphorylation, phosphorylation and activity of Akt, and eNOS phosphorylation in PHT gastric mucosa to normal levels. Furthermore, TNF-alpha stimulated eNOS phosphorylation in human microvascular endothelial cells. In conclusion, these findings show that in PHT gastric mucosa, TNF-alpha stimulates eNOS phosphorylation at serine 1177 (required for its activation) via the PI 3-kinase-Akt signal transduction pathway.     

The assessment of neural injury following open heart surgery by physiological tremor analysis

Introduction

The appearance of post-operative cognitive dysfunction as a result of open heart surgery has been proven by several studies. Focal and/or sporadic neuron damage emerging in the central nervous system may not only appear as cognitive dysfunction, but might strongly influence features of physiological tremor.

Material and methods

We investigated 110 patients (age: 34-73 years; 76 male, 34 female; 51 coronary artery bypass grafting (CABG), 25 valve replacement, 25 combined open heart surgery, 9 off-pump CABG) before surgery and after open-heart surgery on the 3^rd to 5^th post-operative day. The assessment of the physiological tremor analysis was performed with our newly developed equipment based on the Analog Devices ADXL 320 JPC integrated accelerometer chip. Recordings were stored on a PC and spectral analysis was performed by fast Fourier transformation (FFT). We compared power integrals in the 1-4 Hz, 4-8 Hz and 8-12 Hz frequency ranges and these were statistically assessed by the Wilcoxon rank correlation test.

Results

We found significant changes in the power spectrum of physiological tremor. The spectrum in the 8-12 Hz range (neuronal oscillation) decreased and a shift was recognised to the lower spectrum (p < 0.01). The magnitude of the shift was not significantly higher for females than for males (p < 0.157). We found no significant difference between the shift and the cross-clamp or perfusion time (p < 0.6450).

Conclusions

The assessment of physiological tremor by means of our novel, feasible method may provide a deeper insight into the mechanism of central nervous system damage associated with open heart surgery.     

Association between autoimmune pancreatitis and systemic autoimmune diseases

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4).METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT).RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sjögren’s syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto’s thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level.CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.