Computer-Assisted Algorithm for Quantification of Fibrosis by Native Cardiac CT: A Pilot Study.

Background/Objectives: Recent advances in artificial intelligence, particularly in cardiac imaging, can potentially enhance patients' diagnosis and prognosis and identify novel imaging markers. We propose an automated, computer-aided algorithm utilizing native cardiac computed tomography (CT) imaging to identify myocardial fibrosis. This study aims to evaluate its performance compared to CMR markers of fibrosis in a cohort of patients diagnosed with breast cancer. Methods: The study included patients diagnosed with early HER2+ breast cancer, who presented LV dysfunction (LVEF < 50%) and myocardial fibrosis detected on CMR at the time of diagnosis. The patients were also evaluated by cardiac CT, and the extracted images were processed for the implementation of the automatic, computer-assisted algorithm, which marked as fibrosis every pixel that fell within the range of 60-90 HU. The percentage of pixels with fibrosis was subsequently compared with CMR parameters. Results: A total of eight patients (n = 8) were included in the study. High positive correlations between the algorithm's result and the ECV fraction (r = 0.59, p = 0.126) and native T1 (r = 0.6, p = 0.112) were observed, and a very high positive correlation with LGE of the LV(g) and the LV-LGE/LV mass percentage (r = 0.77, p = 0.025; r = 0.81, p = 0.015). A very high negative correlation was found with GLS (r = -0.77, p = 0.026). The algorithm presented an intraclass correlation coefficient of 1 (95% CI 0.99-1), p < 0.001. Conclusions: The present pilot study proposes a novel promising imaging marker for myocardial fibrosis, generated by an automatic algorithm based on native cardiac CT images.

Left atrial geometric and functional remodeling parameters measured by cardiac magnetic resonance imaging and outcome prediction in patients with severe aortic stenosis.

BACKGROUND: Emerging studies are beginning to describe the role of afflicted left atrium (LA) function and strain in cardiovascular diseases including aortic stenosis (AS), especially for risk stratification and outcome prediction. Cardiac magnetic resonance imaging (CMR) is becoming increasingly useful in determining LA parameters; however, in patients with AS, this approach has not been applied yet. AIMS: This study sought to evaluate the role of CMR in characterizing LA geometry and function in patients with severe AS. METHODS: We prospectively evaluated 70 patients with symptomatic severe AS and 70 controls. LA volumes, function, and strain were determined using CMR. A composite outcome (cardiac death, ventricular tachyarrhythmias, and heart failure hospitalization) was evaluated over a median of 13 months. Time-to-event outcomes were analyzed accordingly. RESULTS: Besides increased LA volumes (LAVs) and LA sphericity index (LASI) (P <0.001), LA phasic functions and strain were considerably defective in patients with AS (all P <0.001). LV mass (LVM), end-diastolic and end-systolic volumes were also significantly associated withal LA strain parameters (P <0.001). Regarding outcome prediction, decreased total (LA-εt), active (LA-εa), and passive strain (LA-εp), along with enhanced LASI were independently associated with outcome (P <0.001). Time-to-event analysis showed a significantly higher risk to reach the composite outcome for LA-εt <31.1% (hazard ratio [HR], 6.981; 95% confidence interval [CI], 2.74-17.77; P <0.001), LA-εp <14.5% (HR, 2.68; 95% CI, 1.00-7.18; P <0.01), and LA-εa <21.2% (HR, 2.02; 95% CI, 1.07-3.83, P <0.03). CONCLUSION: Patients with severe AS have a significantly remodeled LA, with impaired phasic function and strain. Amongst all CMR parameters, LAVmin, LASI, LAPF, and LA-εp appear to be independent predictors for outcomes.

Nanoparticles Targeting the Molecular Pathways of Heart Remodeling and Regeneration.

Cardiovascular diseases are the main cause of death worldwide, a trend that will continue to grow over the next decade. The heart consists of a complex cellular network based mainly on cardiomyocytes, but also on endothelial cells, smooth muscle cells, fibroblasts, and pericytes, which closely communicate through paracrine factors and direct contact. These interactions serve as valuable targets in understanding the phenomenon of heart remodeling and regeneration. The advances in nanomedicine in the controlled delivery of active pharmacological agents are remarkable and may provide substantial contribution to the treatment of heart diseases. This review aims to summarize the main mechanisms involved in cardiac remodeling and regeneration and how they have been applied in nanomedicine.

Glioblastoma Microenvironment and Cellular Interactions.

The central nervous system (CNS) represents a complex network of different cells, such as neurons, glial cells, and blood vessels. In tumor pathology, glial cells result in the highest number of cancers, and glioblastoma (GB) is considered the most lethal tumor in this region. The development of GB leads to the infiltration of healthy tissue through the interaction between all the elements of the brain network. This results in a GB microenvironment, a complex peritumoral hallo composed of tumor cells and several non-tumor cells (e.g., nervous cells, stem cells, fibroblasts, vascular and immune cells), which might be the principal factor for the ineffective treatment due to the fact that the microenvironment modulates the biologic status of the tumor with the increase in its evasion capacity. Crosstalk between glioma cells and the brain microenvironment finally inhibits the beneficial action of molecular pathways, favoring the development and invasion of the tumor and its increasing resistance to treatment. A deeper understanding of cell-cell interactions in the tumor microenvironment (TME) and with the tumor cells could be the basis for a more efficient therapy.

Multiple Faces of the Glioblastoma Microenvironment.

The tumor microenvironment is a highly dynamic accumulation of resident and infiltrating tumor cells, responsible for growth and invasion. The authors focused on the leading-edge concepts regarding the glioblastoma microenvironment. Due to the fact that the modern trend in the research and treatment of glioblastoma is represented by multiple approaches that target not only the primary tumor but also the neighboring tissue, the study of the microenvironment in the peritumoral tissue is an appealing direction for current and future therapies.

Cardiotoxicity in HER2-positive breast cancer patients.

Due to the recent advances in diagnosis and management of patients with HER2-positive breast cancer, especially through novel HER2-targeted agents, cardiotoxicity becomes an emerging problem. Although chemotherapy significantly increases survival, the risk of cardiovascular disease development is high and still underestimated and could imply treatment discontinuation. Frequently, due to lack of rigorous diagnosis strategies, cardiotoxicity assessment is delayed, and, moreover, the efficacy of current therapy options in restoring heart function is questionable. For a comprehensive risk assessment, it is vital to characterize the clinical spectrum of HER2-targeted agents and anthracyclines, as well as their pathogenic pathways involved in cardiotoxicity. Advanced cardiovascular multimodal imaging and circulating biomarkers plays primary roles in early assessing cardiotoxicity and also in guiding specific preventive measures. Even though the knowledge in this field is rapidly expanding, there are still questions that arise regarding the optimal approach in terms of timing and methods. The aim of the current review aims to providean overview of currently available data.

Epidermal Growth Factor Receptor and Its Role in Pancreatic Cancer Treatment Mediated by Nanoparticles.

Pancreatic adenocarcinoma (PDAC) is a disease with a high incidence and a dreary prognosis. Its lack of symptomatology and late diagnosis contribute to the dearth and inefficiency of therapeutic schemes. Studies show that overexpressed epidermal growth factor receptor (EGFR) is a common occurrence, linking this to the progression of pancreatic cancer, although the association between its expression and the survival rate is rather controversial. EGFR-targeted therapy has not shown the results expected, leaving at hand more questions than answers; clearly, there is a need for a better understanding of the molecular pathways involved. Nanoparticles have been used in trying to improve the efficacy of antitumor treatment; thus, using EGFR's ligand, EGF, for nanoconjugation, showed promising results in increasing the cellular uptake mechanisms and apoptosis of the targeted cells.

Nanotechnology in metastatic cancer treatment: Current Achievements and Future Research Trends.

The systemic spread of malignant cells from a primary site, a process termed metastasis represents a global challenge in cancer treatment. There is a real need to develop novel therapy strategies and nanomedicine may have remarkable and valuable contribution through specific and selective delivery of chemotherapeutic agents, through its intrinsic cytotoxic activity or through imaging applications, appealing also in the context of cancer personalized therapy. This review is focused on the applications of nanoparticles in the treatment of metastatic cancer, particularly on the possible effect on cell stabilization, growth inhibition, eventual interaction with adhesion molecules and antiangiogenic effect.

Laser thermal ablation of multidrug-resistant bacteria using functionalized gold nanoparticles.

The issue of multidrug resistance (MDR) has become an increasing threat to public health. One alternative strategy against MDR bacteria would be to construct therapeutic vectors capable of physically damaging these microorganisms. Gold nanoparticles hold great promise for the development of such therapeutic agents, since the nanoparticles exhibit impressive properties, of which the most important is the ability to convert light into heat. This property has scientific significance since is exploited to develop nano-photothermal vectors to destroy bacteria at a molecular level. The present paper summarizes the latest advancements in the field of nanotargeted laser hyperthermia of MDR bacteria mediated by gold nanoparticles.

Selective in vitro photothermal nano-therapy of MRSA infections mediated by IgG conjugated gold nanoparticles.

There are serious systemic infections associated with methicillin-resistant Staphylococcus aureus (MRSA) and several other types of bacteria leading to the deaths of millions of people globally. This type of mortality is generally caused by the increasing number of antibiotic-resistant organisms, a consequence of evolution via natural selection. After the synthesis of gold nanoparticles (GNPs) by wet chemistry, bio-functionalization with IgG molecules was performed. Following administration of IgG-GNPs to MRSA cultures at various concentrations and various incubation time laser irradiation was performed. To assess the selectivity and specificity of the proposed treatment the following methods were used: flow cytometry, contrast phase microscopy, and by fluorescence microscopy. The results in our study indicate that following administration of IgG-GNPs biomolecule an extended and selective bacterial death occurs following laser irradiation in a dose dependent manner. Therefore, the new findings might impel studies on these antibacterial nanomaterials and their biological and medical applications.