Two oral antiplatelet agents have been recently introduced for acute coronary syndromes indication providing alternatives for dual therapy with aspirin and clopidogrel. In fact, worldwide prasugrel ...has been on the market for four years, and ticagrelor for over two years. Despite declared benefits over clopidogrel, including hypothetical cost saving advantages, in real life, the clinical utilisation of both agents is small. Generic clopidogrel, and price differences are claimed as major obstacles to prevent broader prasugrel and ticagrelor use. However, these economic difficulties are barely supported by available evidence, and served mostly to protect questionable management spending, as an exuse to explain why in reality cardiologists are so sceptical about both novel agents, and to convince the sharehoders that their money is not wasted, misleading the owners with regard to future success. Importantly, brand Plavix® is used worldwide 5-10 times more often than new agents, despite heavy generic competition. The future of prasugrel outside Japan, where much lower reasonable dose will be used is not impressive due to lack of further outcome studies, negative results of the latest trials, and less than four years left before patent expiration. The fate of ticagrelor will depend on verification of deaths numbers in the ongoing United States Department of Justice PLATO investigation, and confirmation of the mortality benefit in the PEGASUS TIMI-54 trial.
Mechanical properties of cells are important features that are tightly regulated and are dictated by various pathologies. Deformability cytometry allows for the characterization of the mechanical ...properties at a rate of hundreds of cells per second, opening the way to differentiating cells via mechanotyping. A remaining challenge for detecting and classifying rare sub-populations is the creation of a combined experimental and analysis protocol that approaches the maximum potential classification accuracy for single cells. In order to find this maximum accuracy, we designed a microfluidic channel that subjects each cell to repeated deformations and relaxations and provides a comprehensive set of mechanotyping parameters. We track the shape dynamics of individual cells with high time resolution and apply sequence-based deep learning models for feature extraction. In order to create a dataset based solely on differing mechanical properties, a model system was created with treated and untreated HL60 cells. Treated cells were exposed to chemical agents that perturb either the actin or microtubule networks. Multiple recurrent and convolutional neural network architectures were trained using time sequences of cell shapes and were found to achieve high classification accuracy based on cytoskeletal properties alone. The best model classified two of the sub-populations of HL60 cells with an accuracy over 90%, significantly higher than the 75% we achieved with traditional methods. This increase in accuracy corresponds to a fivefold increase in potential enrichment of a sample for a target population. This work establishes the application of sequence-based deep learning models to dynamic deformability cytometry.
In this dissertation, methods for characterizing cells based on their mechanical phenotypes are described. A novel microfluidic channel design is presented and data are gathered as cells pass through ...undulations in the channel. Deep learning methods are applied to the data in a new approach for classifying cells solely based on their mechanical properties. First, in a supervised deep learning approach, a highly interpretable random forest was created and trained to extract the most influential features for cell classification. Feature attributions of the random forest were uncovered using Shapley values. Analysis of the most influential features revealed by the Shapley values highlighted the importance of temporal features, such as the change in aspect ratio over time, in classifying cells. This led to the development of a powerful convolutional recurrent neural network, which dramatically improved classification accuracy to more than 90% when using five-fold cross-validation. Next, an unsupervised deep learning approach for cell classification was explored for problems where classes of cells are unknown a priori. Unsupervised clustering was first tested using manually extracted features and traditional clustering algorithms. However, performance was significantly improved with the development of a variational autoencoder (VAE), which extracted higher-dimensional features. The encoder for the VAE was turned into a classifier using a clustering loss function. This trained network exhibited an accuracy of up to 80% when thresholding the top ~10% of the predictions.
Purpose The present study was undertaken to test bioresorbable fixation versus titanium for equivalence in terms of clinical union and complications using the American Association of Oral and ...Maxillofacial Surgeons parameters of care. The study design was a randomized, controlled, equivalence trial. Materials and Methods A total of 40 patients were enrolled and allocated to the titanium group and bioresorbable group using a computerized randomization table. All were plated using standard plating principles. In the bioresorbable group, 2 weeks of maxillomandibular fixation was also used. Evaluation of the study endpoint was done at 8 weeks postoperatively. For statistical analysis, the upper limit of the 95% confidence interval was calculated for failure to achieve the primary outcome variable and compared with the maximal clinically acceptable difference between the standard and test modalities in the failure to achieve clinical union (δ). δ was predetermined as 2%. The other complications were tested for significance using Fisher's exact test. Results Of the 40 patients, 21 were in the titanium group and 19 were in the bioresorbable group, with 20 men and 1 woman in the titanium group and 18 men and 1 woman in the bioresorbable group. The mean age was 28.7 years in the titanium group and 26.6 years in the bioresorbable group. In the titanium group, the complications noted were nonunion in 0%, malocclusion in 7.7%, continued postoperative swelling in 0%, chronic pain in 2%, infection in 5.2%, an inability to chew hard food after 8 weeks in 7.7%, the need for alternative treatment in 0%, and the need for reoperation in 31%. In the bioresorbable group, the complications were nonunion in 4.17%, malocclusion in 11.1%, swelling in 8.3%, chronic pain in 37.5%, infection in 0%, an inability to chew hard food in 11.1%, the need for alternative treatment in 11.1%, and need for reoperation for plate removal in 0%. Conclusions The small sample size did not allow any meaningful conclusion to be drawn from the present study in terms of the primary question of achieving union. Both groups matched in outcomes when evaluated only on a clinical basis. The avoidance of repeat surgery for plate removal is a definite advantage of using resorbable plates. However, the results are inconclusive in favor of any particular plating system.
The thoracoabdominal region consists of the inferior thorax and superior abdomen and is separated by the diaphragm. Although the diaphragm appears to act as a barrier in this region, various lesions ...can straddle across the diaphragm and lie contiguously in both the thorax and the abdomen. Thoracoabdominal lesions can extend across the diaphragm either through its various natural openings or through abnormal defects. The natural openings lie in the midline and include the hiatuses for the inferior vena cava, the esophagus, and the retrocrural space, which includes the aortic hiatus and the prevertebral and paravertebral spaces. Abnormal defects include congenital defects in fusion, that is, foramina of Morgagni and Bochdalek and acquired diaphragmatic rupture. Very large lesions can also displace the diaphragm, either inferiorly or superiorly, and thus appear to pseudoextend across this region. Using a pattern approach based on the location and route of extension, thoracoabdominal lesions can be classified as central and lateral lesions. Central lesions form a large group, and based on their location, they can be further classified as central anterior, central tendon, inferior vena cava, esophageal, and retrocrural pathologies. Both central and lateral thoracoabdominal lesions form a diverse spectrum and can be congenital, neoplastic, inflammatory, iatrogenic, or traumatic in etiology. Morphologically, these can consist of solid masses, cystic lesions, and ill-defined collections extending across the diaphragm. This article depicts the imaging appearance of the wide spectrum of lesions straddling across the diaphragm. Familiarity with these pathologies can help in better understanding the continuum formed by the thoracoabdominal region and the various routes of transdiaphragmatic extension.
Abstract Purpose To evaluate prospectively the role and impact of multidetector row computed tomography (MDCT) before bronchial artery embolization (BAE) in patients with hemoptysis. Methods MDCT of ...the thorax was performed in 27 patients (21 men, 6 women; age range, 22-70 years; mean, 39 years) with hemoptysis who were referred for BAE. Transverse, multiplanar reconstruction, and 3-dimensional reconstruction (maximum intensity projection and volume rendered) images were analysed to identify the abnormal hypertrophied bronchial and nonbronchial systemic arteries causing hemoptysis, their origin and course were noted. Digital subtraction angiography was performed with the knowledge of findings of MDCT. Selective arteriogram of abnormal bronchial as well as nonbronchial arteries was performed. Embolization was attempted in 25 of these patients (92.6%) by using polyvinyl alcohol particles (350-500 μm), Gelfoam or Embospheres (400-700 μm). Follow-up was done for a mean period of 20.5 months. Results Based on MDCT, 2 of 27 patients were found unsuitable for BAE. On computed tomography, 38 arteries (27 bronchial and 11 nonbronchial systemic arteries) were identified as abnormal hypertrophied vessels. On angiography, 34 of these arteries (25 bronchial and 9 nonbronchial systemic arteries) were found to be responsible for hemoptysis. Three of these arteries could not be evaluated during angiography, and 1 artery that was identified as abnormal on computed tomography was found normal on angiography. All 25 bronchial and 9 nonbronchial systemic arteries that cause hemoptysis were detected at MDCT. Embolization was successful in 23 of 25 patients. Conclusion MDCT enables detection and depiction of all bronchial and nonbronchial systemic arteries causing hemoptysis.
Objective To evaluate the mandibular canal using volume interpolated breath-hold examination (VIBE) sequencing in patients with cysts and tumors of the mandible. Materials and Methods Twenty-five ...patients with mandibular cysts and tumors were recruited for a study in the authors' institution to compare the role of multidetector row computed tomography with magnetic resonance imaging (MRI) in jaw lesions. Of these 25 patients, VIBE was performed in 12 patients (age range, 16 to 52 yrs; 11 male and 1 female patients) and formed the study group. The status (normal/destroyed/attenuated) and position of the inferior alveolar canal (normal/displaced) on panoramic reconstructed computed tomographic (CT) images and curved multiplanar reformatted (MPR) images reconstructed from VIBE images were analyzed. The contralateral normal mandibular canal was used as the control in these patients. Results In all 12 patients, the inferior alveolar canal on the normal side was visualized as a hyperintense structure in relation to the hypointense bone on the curved MPR VIBE images. In 9 patients, the inferior alveolar canal was equally well visualized on panoramic CT and curved MPR VIBE images. In 2 patients, the inferior alveolar canal was better visualized on curved MPR VIBE images; in 1 patient, the course of the mandibular canal was better seen on panoramic CT images. Conclusions MR reconstructions with VIBE sequencing as source images provide images comparable to CT reconstructed images for evaluation of the mandibular canal. Three-dimensional (3D) VIBE sequencing can be added to the MR protocol to visualize the inferior alveolar neurovascular bundle. 3D VIBE sequencing increases the diagnostic capabilities of MRI when used to image mandibular cysts and tumors.
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