Coronary computed tomography angiography (CCTA) has emerged as the preferred modality in the diagnosis of coronary artery disease, but it is limited by modest specificity. By applying principles of computational fluid dynamics, flow fraction reserve, a measure of lesion-specific ischemia that is used to guide revascularization, can be noninvasively derived from CCTA, the so-called computed tomography-derived flow fractional reserve (FFRCT). The accuracy of FFRCT in discriminating ischemia has been extensively validated, and it has been shown to improve the specificity of CCTA. Compared to other stress myocardial perfusion imaging, FFRCT has superior or comparable accuracy. Clinical studies have provided strong evidence that FFRCT has significant prognostic implications and informs clinical decisions for revascularization, serving as a gatekeeper to invasive coronary angiography. In addition, FFRCT-based tools can be used to simulate the physiological consequences of different revascularization strategies, thus providing the roadmap to achieve complete revascularization. Although challenges remain, ongoing research and randomized controlled trials are expected to address current limitations and better define its role in clinical practice.
Secondary mitral regurgitation (MR) refers to MR resulting from left ventricular or left atrial remodeling. In ischemic or nonischemic cardiomyopathy, left ventricular dilation (regional or global) leads to papillary muscle displacement, tethering, and leaflet malcoaptation. In atrial functional MR, MR occurs in patients with left atrial dilation and altered mitral annular geometry due to atrial fibrillation. In addition to cardiac remodeling, leaflet remodeling is increasingly recognized. Mitral leaflet tissue actively adapts through leaflet growth to ensure adequate coaptation. Leaflets, however, can also undergo maladaptive thickening and fibrosis, leading to increased stiffness. The balance of cardiac and leaflet remodeling is a key determinant in the development of secondary MR. Clinical management starts with detection, severity grading, and identification of the underlying mechanism, which relies heavily on echocardiography. Treatment of secondary MR consists of guideline-directed medical therapy, surgical repair or replacement, and transcatheter edge-to-edge repair. Based on a better understanding of pathophysiology, novel percutaneous mitral repair and replacement devices have been developed and clinical trials are underway.
Research in the field of biochemistry and cellular biology has entered a new phase due to the discovery of phase separation driving the formation of biomolecular condensates, or membraneless organelles, in cells. The implications of this novel principle of cellular organization are vast and can be applied at multiple scales, spawning exciting research questions in numerous directions. Of fundamental importance are the molecular mechanisms that underly biomolecular condensate formation within cells and whether insights gained into these mechanisms provide a gateway for accurate predictions of protein phase behavior. Within the last six years, a significant number of predictors for protein phase separation and condensate localization have emerged. Herein, we compare a collection of state-of-the-art predictors on different tasks related to protein phase behavior. We show that the tested methods achieve high AUCs in the identification of biomolecular condensate drivers and scaffolds, as well as in the identification of proteins able to phase separate in vitro. However, our benchmark tests reveal that their performance is poorer when used to predict protein segments that are involved in phase separation or to classify amino acid substitutions as phase-separation-promoting or -inhibiting mutations. Our results suggest that the phenomenological approach used by most predictors is insufficient to fully grasp the complexity of the phenomenon within biological contexts and make reliable predictions related to protein phase behavior at the residue level.
Abstract Background Chimeric antigen receptor T-cell (CAR-T) therapy is a novel immunotherapy for treating hematological malignancies. CAR-T therapy starts with the collection of T-cells from patients. Then, receptors on the T-cell membrane are re-engineered to become chimeric antigen receptors that specifically target antigens on the surface of malignant cells. These engineered cells are grown ex vivo and infused back into the patient, leading to a targeted immune response against cancer. While CAR-T therapy has shown promising results in treating malignancies refractory to conventional treatment, there have also been reports of complications from unwanted off-target effects with CAR-T therapy. Aims We report a case of sclerosing cholangitis secondary to CAR-T therapy for the treatment of mantle cell lymphoma. Methods Case report. Results A 67-year-old male with refractory stage IVB mantle cell lymphoma underwent CAR-T therapy. His lymphoma was first diagnosed in 2011 and previous treatment included R-CHOP followed by autologous stem cell transplant. He had disease progression despite rituximab maintenance therapy and was switched to ibrutinib therapy with good response until 2023. In 2023, he was noted to have progression of his lymphoma. He subsequently underwent CAR-T therapy. His treatment was complicated by grade 2 cytokine release syndrome requiring two doses of tocilizumab. Other complications included immune effector cell-associated neurotoxicity syndrome leading to status epilepticus. He was intubated and required monitoring in the ICU however he was not in shock, nor did he require vasopressors. Post-CAR-T therapy he developed an increase of his liver enzymes in a cholestatic pattern. Magnetic resonance cholangiopancreatography (MRCP) showed irregular biliary dilation with beading suggestive of sclerosing cholangiopathy. He subsequently underwent multiple endoscopic retrograde cholangiopancreatography (ERCP) with stent insertions but there were no improvements in his liver enzymes and jaundice. A liver biopsy was performed which showed large bile duct obstruction with extensive cholestasis and some evidence of non-caseating granulomatous inflammation. Given the timing of new sclerosing cholangiopathy post-CAR-T therapy along with multiple other complications related to CAR-T therapy, it was thought this patient developed sclerosing cholangitis secondary to CAR-T therapy. Due to worsening clinical status along with progression of mantle cell lymphoma, he was transitioned to comfort care. Conclusions CAR-T therapy is a novel immunotherapy for the treatment of refractory hematological malignancies. However, complications from the off-target effects of CAR-T therapy can occur. This case highlighted a rare side effect associated with CAR-T therapy. In the future, more research will be needed to further characterize the risks associated with CAR-T therapy. Cholangiogram showing no visible filling defects or obstructive lesion. Funding Agencies None
High intensity focused ultrasound (HIFU), has applications in treating various cancers, such as prostate, liver and breast cancer. In order for HIFU to be effective and efficient it needs to be guided by an imaging modality. While there are several options for guiding HIFU treatment, one of the most promising is ultrasound elastography. Current commercial devices use Brightness-Mode (B-mode) imaging or MRI, and are manual processes. Ultrasound elastography, allows complete automation of HIFU treatment due to the enhanced image, that elastography provides. The elastic image provides more information and less noise. To show that segmentation was possible on elastic images, nine algorithms were implemented in matlab and used on three distinct images for object detection. The three images used, have varying properties regarding object intensity and placement, as well as different noise patterns. Using PSNR, to gauge the effectiveness of each algorithm, it was shown that segmentation was possible on all images using different algorithms. The bilateral-shock-bilateral algorithm proved to be an overall effective algorithm in every situation with a PSNR of 83.87db on the phantom image. The segmentation results clearly highlight any object in the images. Future work includes fine tuning the algorithm with different phantom images and in-vivo images to distinguish between noise and desired object.
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