Medical Radiology: Current Progress

Recently, medical radiology has undergone significant improvements in patient management due to advancements in image acquisition by the last generation of machines, data processing, and the integration of artificial intelligence. In this way, cardiovascular imaging is one of the fastest-growing radiological subspecialties. In this study, a compressive review was focused on addressing how and why CT and MR have gained a I class indication in most cardiovascular diseases, and the potential impact of tissue and functional characterization by CT photon counting, quantitative MR mapping, and 4-D flow. Regarding rectal imaging, advances in cancer imaging using diffusion-weighted MRI sequences for identifying residual disease after neoadjuvant chemoradiotherapy and [18F] FDG PET/MRI were provided for high-resolution anatomical and functional data in oncological patients. The results present a large overview of the approach to the imaging of diffuse and focal liver diseases by US elastography, contrast-enhanced US, quantitative MRI, and CT for patient risk stratification. Italy is currently riding the wave of these improvements. The development of large networks will be crucial to create high-quality databases for patient-centered precision medicine using artificial intelligence. Dedicated radiologists with specific training and a close relationship with the referring clinicians will be essential human factors

TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis

BACKGROUND: TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place. METHODS: In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects. RESULTS: Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1. CONCLUSIONS: These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease

ALMS1-Deficient Fibroblasts Over-Express Extra-Cellular Matrix Components, Display Cell Cycle Delay and Are Resistant to Apoptosis

Alström Syndrome (ALMS) is a rare genetic disorder (483 living cases), characterized by many clinical manifestations, including blindness, obesity, type 2 diabetes and cardiomyopathy. ALMS is caused by mutations in the ALMS1 gene, encoding for a large protein with implicated roles in ciliary function, cellular quiescence and intracellular transport. Patients with ALMS have extensive fibrosis in nearly all tissues resulting in a progressive organ failure which is often the ultimate cause of death. To focus on the role of ALMS1 mutations in the generation and maintenance of this pathological fibrosis, we performed gene expression analysis, ultrastructural characterization and functional assays in 4 dermal fibroblast cultures from ALMS patients. Using a genome-wide gene expression analysis we found alterations in genes belonging to specific categories (cell cycle, extracellular matrix (ECM) and fibrosis, cellular architecture/motility and apoptosis). ALMS fibroblasts display cytoskeleton abnormalities and migration impairment, up-regulate the expression and production of collagens and despite the increase in the cell cycle length are more resistant to apoptosis. Therefore ALMS1-deficient fibroblasts showed a constitutively activated myofibroblast phenotype even if they do not derive from a fibrotic lesion. Our results support a genetic basis for the fibrosis observed in ALMS and show that both an excessive ECM production and a failure to eliminate myofibroblasts are key mechanisms. Furthermore, our findings suggest new roles for ALMS1 in both intra- and extra-cellular events which are essential not only for the normal cellular function but also for cell-cell and ECM-cell interactions

Challenging cases of aortic prosthesis dysfunction, the importance of multimodality imaging, a case series

ECG-gated multidetector computed tomography (MDCT) is a promising complementary technique for evaluation of cardiac native and prosthetic structures. MDCT is able to provide a broader coverage with faster scan acquisition times that yield higher spatial and temporal resolution for cardiac structures whose quality may be affected by artifacts on ultrasound. We report a case series about the most challenging complications occurring after prosthetic aortic valve implantation in four patients: pannus, paravalvular leak, prosthesis’ misfolding and subaortic membrane reformation. In all the cases, enhanced MDCT using a retrospective protocol provided accurate 3D morphoanatomic information about cardiac and extracardiac structures, improving and speeding up the correct diagnosis and treatment planning. Integrated imaging, in particular with MDCT, is now the present, and it will increasingly be the future in the assessment of cardiac structural pathology

Diagnostic Accuracy of CT Texture Analysis in Adrenal Masses: A Systematic Review

Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and malignancy (primary or metastatic disease) are assessed at baseline evaluation. Size, lipid content, and washout charac-terise benign AIs (respectively, <4 cm, <10 Hounsfield unit, and rapid release); nonetheless, 30% of adrenal lesions are not correctly indicated. Recently, image-based texture analysis from computed tomography (CT) may be useful to assess the behaviour of indeterminate adrenal lesions. We performed a systematic review to provide the state-of-the-art of texture analysis in patients with AI. We considered 9 papers (from 70 selected), with a median of 125 patients (range 20–356). Histological confirmation was the most used criteria to differentiate benign from the malignant adrenal mass. Unenhanced or contrast-enhanced data were available in all papers; TexRAD and PyRadiomics were the most used software. Four papers analysed the whole volume, and five considered a region of interest. Different texture features were reported, considering first-and second-order statistics. The pooled median area under the ROC curve in all studies was 0.85, depicting a high diagnostic accuracy, up to 93% in differentiating adrenal adenoma from adrenocortical carcinomas. Despite heterogeneous methodology, texture analysis is a promising diagnostic tool in the first assessment of patients with adrenal lesions

Percutaneous closure of patent foramen ovale and secundum atrial septal defects with the gore® cardioform septal occluder: Incidence and implications of device wire frame fracture

Background: Trans-catheter closure has become the treatment of choice for patent foramen ovale (PFO) and ostium secundum atrial septal defects (ASD). A wide variety of devices are commercially available, however, concerns have been raised about the risk of cardiac erosion associated with stiff/rigid devices. The GORE® CARDIOFORM Septal Occluder (GSO) is a double-disc, soft and conformable device with no reported incidence of cardiac erosions. How-ever, wire frame fracture (WFF) have been reported. Aim: To assess the incidence and clinical significance of WFF after GSO implantation in paediatric patients. Methods: Seventy-seven consecutive patients were enrolled. Periprocedural and follow-up assessments included clinical, echocardiographic, and X-ray fluoro-scopy examinations. Results: Mean patient age was 10.0 ± 3.9 years. In 7 patients the indication was PFO closure, in 70 patients ASD closure. Mean follow-up period was 3.1 ± 1.3 years. X-ray fluoroscopy evaluations were available for 60 patients. WFF was detected in a total of 22 (35.4%) GSO devices. Three WFF compromised the outer perimeter of the device. Incidence of WFF was higher for the 30 mm GSO device (58%; p = 0.001). A multivariate analysis confirmed that the GSO device diameter (p = 0.013; F = 6.7) and stretched ASD diameter (p = 0.034; F = 4.38) were independent factors related to WFF. WFF did not result in any clinical sequelae/patient harm. Residual shunt was observed in 4 patients (5%) at 24 hours following procedure. Conclusion: The GSO device is safe and effective for PFO and ASD closure. WFF was not associated with clinical sequelae or device instability. Device diameter strongly correlates with incidence of WFF

Membrane form of TNF alfa induces both cell lysis and apoptosis in susceptible target cells.

Tumor necrosis factor alpha, in the secreted as well as membrane-associated (mTNF alpha) form, represents a cytotoxic effector mechanism of activated macrophages; in contrast, direct evidence of the mTNF alpha involvement in cytotoxic T lymphocyte (CTL)-mediated lysis has not yet been obtained. We observed that following activation with anti-CD3 monoclonal antibody (mAb), both cloned CTL and peritoneal exudate lymphocytes rapidly upregulated mTNF alpha; a similar effect was observed in the macrophage cell line J774 after stimulation with lipopolysaccharide endotoxin. Activated effector cells, which were fixed with paraformaldehyde before testing, exerted lytic activity against the TNF-sensitive WEHI 164 tumor cell line, but not against the TNF-resistant P-815 mastocytoma. This effect was completely inhibited in the presence of anti-mouse TNF alpha Ab. Moreover, both mTNF alpha-expressing macrophages and CTL induced nuclear DNA fragmentation in WEHI 164 cells, which was also blocked by anti-TNF alpha Ab and was accompanied by a morphologic degeneration characteristic of the apoptotic form of cell death. These data on the whole indicate a common mode of action for mTNF alpha expressed on different cell populations endowed with cytotoxic capability and also imply a role for this molecule in T-cell-mediated cytotoxicity

Inhibition of ShcA isoforms p46/p52Shc enhances HIV-1 replication in CD4+ T-lymphocytes

HIV-1 infection decreases the number of CD4þ T-cells, and apoptosis has been suggested among the mechanisms. Proteins of the Shc family are involved in a complex network of signal transduction, differentiation, and apoptotic response to stress in many different cell types. Out of three homologous gene products (ShcA, ShcB, and ShcC), only two splicing variants of ShA are expressed in T-lymphocytes, namely p46Shc and p52Shc. In the present study, we report that inhibition of p46Shc and p52Shc by a dominant negative mutant enhances the yield of HIV-1 particles production without affecting efficiency of viral gene expression in CD4þ- infected cells. The increase in HIV-1 replication in cells expressing the dominant negative mutant isoform ultimately correlates with a decrease in the percentage of cells entering apoptosis. The data presented suggest that ShcA proteins can play a role in committing CD4þ T-cells to apoptosis, as a response to HIV-1 infection