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Background Chemotherapeutic agents have many side effects; among them is cardiotoxicity. Ejection fraction fails to detect the subtle alterations of left ventricular (LV) function; that is why there is a need for a more sensitive tool. The aim is to detect subclinical LV systolic dysfunction after chemotherapeutic treatment, using NT-BNP plasma level as well as speckle tracking echo-global longitudinal strain (STE-GLS). Seventy-four asymptomatic, non-metastasizing breast cancer female patients without risk factors were included. They were assessed before and 6 weeks after taking their first chemotherapeutic session. Assessment included clinical characteristics, conventional two-dimensional (2D) and three-dimensional (3D) echocardiography, and 2D STE-GLS. Blood samples for NT-BNP plasma level were collected on both visits and were later analyzed using a Sandwich ELISA technique. Results The median NT-proBNP almost doubled after 6 weeks of chemotherapy (73.50 vs 34.4 pg/L, p value <0.001). Only two patients showed significant reduction of LVEF >10% to less <55%. One patient died before her scheduled follow-up visit, and the cause of death is unknown. Fifty patients showed elevated follow-up levels of the NT-BNP. As compared to the baseline visit, 12 patients had a high relative reduction of the LV-GLS (>15%) and all of them had a relatively higher NT-proBNP. A 2.2 relative elevation of the NT-proBNP was able to define a relative reduction of LV-GLS >15% by a 100% sensitivity and 81.8% specificity. Conclusion The relative reduction of LV-GLS and the relative elevation of NT-proBNP were successful in defining subclinical, subtle chemotherapy-induced cardiotoxicity after 6 weeks of the first chemotherapeutic agent administration.

BackgroundRheumatoid arthritis (RA) is associated with elevated plasma level of inflammatory markers. Chronic inflammation is known to predispose to endothelial dysfunction and increased arterial stiffness, which is an important marker of subclinical atherosclerosis and increased cardiovascular risk.ObjectiveThe aim is to test for the relationship between disease activity and arterial stiffness in RA patients.MethodsThe study included 90 RA patients, at different grades of disease activity and 45 healthy subjects, as a control group. Patients were subjected to full history taking and clinical examination, laboratory investigations including serum lipid profile and high sensitivity CRP (hs-CRP) measurements and plain x-rays of hands and feet. Modified Larsen method was used as radiographic scoring method. Disease activity score (DAS 28) was used for assessment of disease activity. Transthoracic echocardiography was performed to detect aortic stiffness parameters. Duplex ultrasound imaging of both common carotid arteries was performed to measure carotid stiffness parameters.ResultsThe mean age of RA patients was 39.86 ± 9.39 years and most of them (83.3%) were females. RA patients had higher carotid stiffness index compared to control group patients (8.57 ± 4.83 vs 4.08 ± 1.13, p < .001). Very poor correlation was found between DAS-28 and aortic (r = 0.1, p = .28) as well as carotid (r = 0.05, p = .7) stiffness indices. No statistically significant correlation was found between hs-CRP and aortic stiffness index (r = 0.64, p = .55). Disease duration was significantly correlated to intima-media thickness (p < .01) as well as with other carotid stiffness parameters. Age also show a statistically significant positive correlation with carotid stiffness parameters.ConclusionRA is associated with increased arterial stiffness, a well-recognized marker of cardiovascular risk. This is attributed to the inflammatory nature of the disease. It seems that the most important factors determining stiffness are patients' age and duration of illness.

Purpose Protein misfolding and aggregation result in proteotoxic stress and underlie the pathogenesis of many diseases. To overcome proteotoxicity, cells compartmentalize misfolded and aggregated proteins in different inclusion bodies. The aggresome is a paranuclear inclusion body that functions as a storage compartment for misfolded proteins. Choroid plexus tumors (CPTs) are rare neoplasms comprised of three pathological subgroups. The underlying mechanisms of their pathogenesis remain unclear. This study aims to elucidate the prognostic role and the biological effects of aggresomes in pediatric CPTs. Methods We examined the presence of aggresomes in 42 patient-derived tumor tissues by immunohistochemistry and we identified their impact on patients’ outcomes. We then investigated the proteogenomics signature associated with aggresomes using whole-genome DNA methylation and proteomic analysis to define their role in the pathogenesis of pediatric CPTs. Results Aggresomes were detected in 64.2% of samples and were distributed among different pathological and molecular subgroups. The presence of aggresomes with different percentages was correlated with patients’ outcomes. The ≥ 25% cutoff had the most significant impact on overall and event-free survival (p-value < 0.001) compared to the pathological and the molecular stratifications. Conclusions These results support the role of aggresome as a novel prognostic molecular marker for pediatric CPTs that was comparable to the molecular classification in segregating samples into two distinct subgroups, and to the pathological stratification in the prediction of patients’ outcomes. Moreover, the proteogenomic signature of CPTs displayed altered protein homeostasis, manifested by enrichment in processes related to protein quality control.

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