Extended thromboprophylaxis with betrixaban in acutely ill medical patients

BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.)

Software for full-color 3D reconstruction of the biological tissues internal structure

A software for processing sets of full-color images of biological tissue histological sections is developed. We used histological sections obtained by the method of high-precision layer-by-layer grinding of frozen biological tissues. The software allows restoring the image of the tissue for an arbitrary cross-section of the tissue sample. Thus, our method is designed to create a full-color 3D reconstruction of the biological tissue structure. The resolution of 3D reconstruction is determined by the quality of the initial histological sections. The newly developed technology available to us provides a resolution of up to 5 - 10 {\mu}m in three dimensions.Comment: 11 pages, 8 figure

PROJECTED LIGHT SYSTEM FOR TRUNK SURFACE RECONSTRUCTION AND VOLUME MEASUREMENT DURING RESPIRATION

There is an increasing interest on developing non invasive and accurate methods to obtain torso shape and deformation during movement. Methods like inductance pletismography (Warren et al. 1989), magnetommetry (Verschakelen & Demedts 1995) and kinematical analysis (Ferrigno et al. 1994) have been proposed to access the pulmonary function based on trunk motion analysis. Measurements of body shape and dimensions are widely used on ergonomic and anthropometry designs fields (Allen et al. 2004) and to estimate body segment parameters for the analysis of human movement (Wicke et al. 2009). The aim of this work was to present a video-based method for trunk volumes measurement during the respiration by means of projected light and surface reconstruction

Complicated Grief: What to Expect After the Coronavirus Pandemic

The COVID-19 pandemic is one of the worst public health crises in a century, with an expected amount of deaths of several million worldwide and an even bigger number of bereaved people left behind. Although the consequences of this crisis are still unknown, a significant number of bereaved people will arguably develop Complicated Grief (CG) in the aftermath of this emergency. If the current pandemic is unprecedented, the grief following the coronavirus outbreak is likely to share features with grief related to natural disasters and after Intensive Care Unit (ICU) treatment. The aim of this paper is to review the most prominent literature on CG after natural disasters, as well as after diseases requiring ICU treatment. This body of evidence may be useful for helping bereaved people during the acute phase of the COVID-19 pandemic and for drawing clinical attention to people at risk for CG

Merging C-C σ-bond activation of cyclobutanones with CO2 fixation via Ni-catalysis

A carboxylative Ni-catalyzed tandem C-C σ-bond activation of cyclobutanones followed by CO2-electrophilic trapping is documented as a direct route to synthetically valuable 3-indanone-1-acetic acids. The protocol shows an adequate functional group tolerance and useful chemical outcomes (yield up to 76%) when AlCl3 is adopted as an additive. Manipulations of the targeted cyclic scaffolds and a mechanistic proposal based on experimental evidence complete the investigation

Deep Learning for Automated Analysis of Cellular and Extracellular Components of the Foreign Body Response in Multiphoton Microscopy Images

The Foreign body response (FBR) is a major unresolved challenge that compromises medical implant integration and function by inflammation and fibrotic encapsulation. Mice implanted with polymeric scaffolds coupled to intravital non-linear multiphoton microscopy acquisition enable multiparametric, longitudinal investigation of the FBR evolution and interference strategies. However, follow-up analyses based on visual localization and manual segmentation are extremely time-consuming, subject to human error, and do not allow for automated parameter extraction. We developed an integrated computational pipeline based on an innovative and versatile variant of the U-Net neural network to segment and quantify cellular and extracellular structures of interest, which is maintained across different objectives without impairing accuracy. This software for automatically detecting the elements of the FBR shows promise to unravel the complexity of this pathophysiological process

Tumor tracking based on correlation models in scanned ion beam therapy: an experimental study

n/

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Predicting vulnerable coronary arteries: A combined radiomics-biomechanics approach

Background and Objective: Nowadays, vulnerable coronary plaque detection from coronary computed tomography angiography (CCTA) is suboptimal, although being crucial for preventing major adverse cardiac events. Moreover, despite the suggestion of various vulnerability biomarkers, encompassing image and biomechanical factors, accurate patient stratification remains elusive, and a comprehensive approach integrating multiple markers is lacking. To this aim, this study introduces an innovative approach for assessing vulnerable coronary arteries and patients by integrating radiomics and biomechanical markers through machine learning methods. Methods: The study included 40 patients (7 high-risk and 33 low-risk) who underwent both CCTA and coronary optical coherence tomography (OCT). The dataset comprised 49 arteries (with 167 plaques), 7 of which (with 28 plaques) identified as vulnerable by OCT. Following image preprocessing and segmentation, CCTA-based radiomic features were extracted and a finite element analysis was performed to compute the biomechanical features. A novel machine learning pipeline was implemented to stratify coronary arteries and patients. For each stratification task, three independent predictive models were developed: a radiomic, a biomechanical and a combined radiomic-biomechanical model. Both k-nearest neighbors (KNN) and decision tree (DT) classifiers were considered. Results: The best radiomic model (KNN) detected all 7 vulnerable arteries and patients and was associated with a balanced accuracy of 0.86 (sensitivity=1, specificity=0.71) for the artery model and of 0.83 (sensitivity=1, specificity=0.67) for the patient model. The best biomechanical model (DT) detected 6 over 7 vulnerable arteries and patients and remarkably increased the specificity, resulting in a balanced accuracy of 0.89 (sensitivity=0.86, specificity=0.93) for the artery model and of 0.88 (sensitivity=0.86, specificity=0.91) for the patient model. Notably, the combined approach optimized the performance, with an increase in the balance accuracy up to 0.94 for the artery model and up to 0.92 for the patient model, being associated with sensitivity=1 and high specificity (0.88 and 0.85 for artery and patient models, respectively). Conclusion: This investigation highlights the promise of radio-mechanical coronary artery phenotyping for patient stratification. If confirmed from larger studies, our approach enables a more personalized management of the disease, with the early identification of high-risk individuals and the reduction of unnecessary interventions for low-risk individuals