Myocardial extracellular volume fraction to differentiate healthy from cardiomyopathic myocardium using dual-source dual-energy CT

Objective: To evaluate the feasibility of dual-energy CT (DECT)-based iodine quantification to estimate myocardial extracellular volume (ECV) fraction in patients with and without cardiomyopathy (CM), as well as to assess its ability to distinguish healthy myocardial tissue from cardiomyopathic, with the goal of defining a threshold ECV value for disease detection. Methods: Ten subjects free of heart disease and 60 patients with CM (mean age 66.4 ± 9.4; 59 males and 11 females; 40 ischemic and 20 non-ischemic CM) underwent late iodine enhanced DECT imaging. Myocardial iodine maps were obtained using 3-material decomposition. ECV of the left ventricle was estimated from hematocrit levels and the iodine maps using the AHA 16-segment model. Receiver operating characteristic curve analysis was performed, with corresponding area under the curve, along with Youden's index assessment, to establish a threshold for CM detection. Results: The median ECV for healthy myocardium, non-ischemic CM, and ischemic CM were 25.4% (22.9–27.3), 38.3% (33.7–43.0), and 36.9% (32.4–41.1), respectively. Healthy myocardium showed significantly lower ECV values compared to ischemic and non-ischemic CM (p 29.5% would indicate the presence of CM in the myocardium (sensitivity = 90.3; specificity = 90.3); the AUC for this criterion was 0.950 (p < 0.001). Conclusion: The findings of this study resulted in a statistically significant distinction between healthy myocardium and CM ECVs. This led to the establishment of a promising threshold ECV value that could facilitate the differentiation between healthy and diseased myocardium, and highlights the potential of this DECT methodology to detect cardiomyopathic tissue

Transplantation of autologous extracellular vesicles for cancer-specific targeting

Nano- and microsized extracellular vesicles (EVs) are naturally occurring cargo-bearing packages of regulatory macromolecules, and recent studies are increasingly showing that EVs are responsible for physiological intercellular communication. Nanoparticles encapsulating anti-tumor theranostics represent an attractive \u201cexosome-interfering\u201d strategy for cancer therapy. Methods: Herein, by labeling plasma-derived EVs with indocyanine green (ICG) and following their biodistribution by in vivo and ex vivo imaging, we demonstrate the existence of nanoparticles with a highly selective cancer tropism in the blood of colorectal cancer (CRC) patients but not in that of healthy volunteers. Results: In CRC patient-derived xenograft (PDX) mouse models, we show that transplanted EVs recognize tumors from the cognate nanoparticle-generating individual, suggesting the theranostic potential of autologous EVs encapsulating tumor-interfering molecules. In large canine breeds bearing spontaneous malignant skin and breast tumors, the same autologous EV transplantation protocol shows comparable safety and efficacy profiles. Conclusions: Our data show the existence of an untapped resource of intercellular communication present in the blood of cancer patients, which represents an efficient and highly biocompatible way to deliver molecules directly to the tumor with great precision. The novel EV-interfering approach proposed by our study may become a new research direction in the complex interplay of modern personalized cancer therapy

The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast

Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. Patients and methods: We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive. Results: Of the 1488 patients with DCIS under study, 35.1% had < 1%, 58.3% 1-49% and 6.5% ≥ 50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95-0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≥ 0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥ 50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥ 50%), no statistically significant association was observed (10- year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767). Conclusion: TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Cross-modality Accuracy of Dual-step, Prospectively Electrocardiography-triggered Dual-source Computed Tomography Compared With Same-day Echocardiography and Cardiac Magnetic Resonance Imaging in the Follow-up of Heart-transplant Patients

Purpose: An accurate evaluation of left ventricular volumes, mass, and ejection fraction (EF) and an early exclusion or detection of significant coronary artery disease or cardiac allograft vasculopathy are mandatory for clinical management and prognosis assessment of heart-transplanted patients (HTP). The purpose of this article was to evaluate the role of dual-step prospective electrocardiographytriggered Dual-Source CT (pECGdual-step-DSCT) in HTP for the assessment of left-ventricular function, in comparison with echocardiography (echo) and cardiac magnetic resonance (CMR) performed on the same day, and of the coronary arteries as well. Materials and Methods: Left-ventricular EF, end-diastolic volume, end-systolic volume, stroke volume, cardiac output (CO), and mass were assessed in 11 HTP by pECGdual-step-DSCT in comparison with CMR and echo performed on the same day. During all the examinations, the heart rate was recorded. CT coronary artery assessment was also performed. Results: Heart rate was lower during DSCT (75.6\ub17.8 bpm; P<0.001). EF resulted slightly lower for DSCT (55.7%\ub15.0%; P 650.05) in comparison with CMR (57.8%\ub15.3%; P 65 0.05) and echo (59.2%\ub15.6%; P 650.05). DSCT showed statistically significant higher end-diastolic volume (153.7\ub124.2 mL), end-systolic volume (67.8\ub111.5 mL), and stroke volume (85.9\ub117.6 mL) (P< 0.01 up to 0.001) than CMR, but with a high correlation (P< 0.001). Cardiac output was almost similar for DSCT versus CMR, with a very high correlation coefficient (r=0.914; P<0.001). DSCT showed higher mass values than CMR (P<0.001), but with a high correlation (r=0.866; P<0.001). DSCT versus echo results were less correlated. No significant coronary artery disease was detected. Conclusion: pECGdual-step-DSCT allows reliable assessment of leftventricular function in HTP, with good agreement and correlation with CMR, within a global diagnostic approach including coronary artery evaluation in one single-volume acquisition