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Multi-center study of inter-rater reproducibility, image quality, and diagnostic accuracy of CZT versus conventional SPECT myocardial perfusion imaging.
Mansour, N, Nekolla, SG, Reyes, E, Angelidis, G, Georgoulias, P, Anagnostopoulos, C, Bravo, P, Bruno, I, Flotats, A, Fuentes-Ocampo, F, et al
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2023;(2):528-539
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Abstract
BACKGROUND Cadmium-zinc-telluride (CZT)-based detectors exhibit higher diagnostic sensitivity in myocardial perfusion imaging (MPI) than conventional Anger-MPI for detection of coronary artery disease (CAD); however, reduced specificity and diagnostic accuracy of CZT-MPI were observed. This study aims to compare these different camera systems and to examine the degree of inter-rater reproducibility among readers with varying experience in MPI. METHODS 83 patients who underwent double stress/rest examinations using both a CZT and conventional SPECT cameras within one visit were included. Anonymized and randomized MPI-images were distributed to 15 international readers using a standardized questionnaire. Subsequent coronary angiography findings of ten patients served as a reference for analysis of sensitivity and specificity. RESULTS Image quality was significantly better in CZT-MPI with significantly lower breast attenuation (P < 0.05). CZT-MPI exhibited higher sensitivity than Anger-MPI (87.5% vs. 62.5%) and significantly reduced specificity (40% vs. 100%). Readers experienced with both camera systems had the highest inter-rater agreement indicating higher reproducibility (CZT 0.54 vs. conv. 0.49, P < 0.05). CONCLUSIONS Higher diagnostic sensitivity of CZT-MPI offers advantages in detection of CAD yet potentially of at the cost of reduced specificity, therefore it requires special training and a differentiated evaluation approach, especially for non-experienced readers with such camera systems.
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Type I spinal muscular atrophy patients treated with nusinersen: 4-year follow-up of motor, respiratory and bulbar function.
Pane, M, Coratti, G, Sansone, VA, Messina, S, Catteruccia, M, Bruno, C, Sframeli, M, Albamonte, E, Pedemonte, M, Brolatti, N, et al
European journal of neurology. 2023;(6):1755-1763
Abstract
BACKGROUND We report the 4-year follow-up in type I patients treated with nusinersen and the changes in motor, respiratory and bulbar function in relation to subtype, age and SMN2 copy number. METHODS The study included SMA 1 patients with at least one assessment after 12, 24 and 48 months from the first dose of nusinersen. The assessments used were Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination (HINE-II). RESULTS Forty-eight patients, with ages ranging from 7 days to 12 years (mean 3.3 years, SD 3.6 years) were included in the study. The CHOP INTEND and HINE-II scores significantly increased between baseline and 48 months (p < 0.001). When age at starting treatment subgroups (<210 days, <2 years, 2-4 years, 5-11 years, ≥12 years) were considered, the CHOP INTEND increased significantly in patients younger than 4 years at treatment, while the HINE-2 increased significantly in patients younger than 2 years at treatment. In a mixed-model analysis, age, nutritional and respiratory status were predictive of changes on both scales while SMN2 copy number and decimal classification were not. CONCLUSIONS Our results confirm the safety profile previously reported and support the durability of the efficacy of nusinersen at 4 years with an overall stability or mild improvement and no evidence of deterioration over a long period of time.
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Discovery of noscapine derivatives as potential β-tubulin inhibitors.
Nemati, F, Salehi, P, Bararjanian, M, Hadian, N, Mohebbi, M, Lauro, G, Ruggiero, D, Terracciano, S, Bifulco, G, Bruno, I
Bioorganic & medicinal chemistry letters. 2020;(20):127489
Abstract
Twenty novel 1,2,3-triazole noscapine derivatives were synthesized starting from noscapine by consecutive N-demethylation, reduction of lactone ring, N-propargylation and Huisgen 1,3-dipolar cycloaddition reaction. In order to select the most promising molecules to subject to further biophysical and biological evaluation, a molecular docking analysis round was performed using noscapine as reference compound. The molecules featuring docking predicted binding affinity better than that of noscapine were then subjected to MTT assay against MCF7 cell line. The obtained results disclosed that all the selected triazole derivatives exhibited a remarkably lower cell viability compared to noscapine in the range of 20 μM in 48 h. In an attempt to correlate the biological activity with the ability to bind tubulin, the surface plasmon resonance (SPR) assay was employed. Compounds 8a, 8h, 9c, 9f and 9j were able to bind tubulin with affinity constant values in the nanomolar range and higher if compared to noscapine. Integrating computational predictions and experimental evaluation, two promising compounds (8h and 9c) were identified, whose relevant cytotoxicity was supposed to be correlated with tubulin binding affinity. These findings shed lights onto structural modifications of noscapine toward the identification of more potent cytotoxic agents targeting tubulin.
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Remnant cholesterol as a risk factor for cardiovascular, cancer or other causes mortality: A competing risks analysis.
Bonfiglio, C, Leone, CM, Silveira, LVA, Guerra, R, Misciagna, G, Caruso, MG, Bruno, I, Buongiorno, C, Campanella, A, Guerra, VMB, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2020;(11):2093-2102
Abstract
BACKGROUND AND AIMS Cardiovascular diseases (CVDis) are leading causes of morbidity and mortality. Even after the introduction of pharmacological therapy to lower Cholesterol, there is still a residual risk that may be ascribed to remnant cholesterol (RC). We aimed, by analyzing two prospective cohort studies, to estimate the effect of RC on risk and hazard of cardiovascular deaths (CVDs), while accounting for competing risks such as cancer (CDs) and other-causes deaths (OCDs). METHODS AND RESULTS Cohorts were enrolled in 1992 and 2005. Personal data history was recorded. A fasting venous blood sample was obtained, and RC was calculated at baseline. Cause of Death was coded by using ICD-10th version. Follow-up ended on December 31, 2017. Flexible parametric competing-risks models were applied, with age at death as time-axis. In total, 5729 subjects were enrolled. There were 861 (15.1%) deaths: 234 CVDs (27.2%), 245 CDs (28.5%), 271 OCDs (31.5%) and 111 unknown causes of death (12.8%). RC exposure was a strong risk factor only for CVDs (Risk 2.54, 95% Confidence Interval 1.21; 5.34; Trend 1.26 (1.00; 1.58) for ≥1.29 mmol/L). CONCLUSIONS RC is a strong independent risk factor for cardiovascular mortality. Competing risk analysis is demonstrably a useful tool to disentangle associations among different competing events with a common risk factor.
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Effects of Some Food Components on Non-Alcoholic Fatty Liver Disease Severity: Results from a Cross-Sectional Study.
Mirizzi, A, Franco, I, Leone, CM, Bonfiglio, C, Cozzolongo, R, Notarnicola, M, Giannuzzi, V, Tutino, V, De Nunzio, V, Bruno, I, et al
Nutrients. 2019;11(11)
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Plain language summary
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic (liver) fat accumulation. Lifestyle interventions are the only known effective treatment for NAFLD. The aim of this study was to estimate associations between the consumption of some food group components with the grade of severity in NAFLD subjects. The study is a cross-sectional nutritional randomised clinical trial, which enrolled 136 subjects (79 males) with moderate or severe NAFLD. Results showed that some food group components were associated with a lower or a higher risk of developing severe NAFLD, and that, within the same food group, some components with a protective or promoter action are present. Authors conclude that their findings could help to elaborate personalised dietary counselling to treat NAFLD.
Abstract
Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) observed in Western countries is due to the concurrent epidemics of overweight/obesity and associated metabolic complications, both recognized risk factors. A Western dietary pattern has been associated with weight gain and obesity, and more recently with NAFLD. Methods: This is a baseline cross-sectional analysis of 136 subjects (79 males) enrolled consecutively in the NUTRIATT (NUTRItion and Ac-TiviTy) study. Study subjects had moderate or severe NAFLD diagnosed by using Fibroscan-CAP. Food Frequency Questionnaire was used to obtain information about food intake. Statistical analysis included descriptive statistics and a multivariable logistic regression model. Results: The mean age was 49.58 (±10.18) with a mean BMI of 33.41 (±4.74). A significant inverse relationship was revealed between winter ice-cream intake and NAFLD severity (O.R. 0.65, 95% C.I. 0.95-0.99); chickpeas intake and NAFLD severity (O.R. 0.57, 95% C.I. 0.34-0.97), and not industrial aged-cheeses type (O.R. 0.85, 95% C.I. 0.74-0.98). A statistically significant positive association also emerged between rabbit meat (O.R. 1.23, 95% C.I. 1.01-1.49), industrial type aged cheeses (O.R. 1.17, 95% C.I. 1.01-1.35), milk-based desserts (no winter ice cream) (O.R. 1.11, 95% C.I. 1.01-1.21), fats (O.R. 1.12, 95% C.I. 1.01-1.25), and NAFLD severity. Conclusion: The fresh foods from non-intensive farming and high legume intake that characterize the Mediterranean diet would seem to be beneficial for patients with NAFLD.
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Glucopyranosylbianthrones from the Algerian Asphodelus tenuifolius: Structural Insights and Biological Evaluation on Melanoma Cancer Cells.
Khalfaoui, A, Chini, MG, Bouheroum, M, Belaabed, S, Lauro, G, Terracciano, S, Vaccaro, MC, Bruno, I, Benayache, S, Mancini, I, et al
Journal of natural products. 2018;(8):1786-1794
Abstract
Two new glucopyranosylbianthrones (1 and 2) were isolated from the aerial part of the plant Asphodelus tenuifolius, collected in Southwest Algeria. The 2D structures of 1 and 2 were defined by NMR analysis, HRESIMS data, and comparison with literature data. The comparison of experimental and calculated electronic circular dichroism and NMR data led to characterization of the ( M) and ( P) atropisomeric forms of the glucopyranosylbianthrones, asphodelins (1) and (2), respectively. The in vitro activities of these two metabolites were evaluated in human melanoma A375 cells, and both the compounds inhibited cell proliferation in a concentration-dependent manner, with IC50 values of 20.6 ± 0.8 and 23.2 ± 1.1 μM, respectively. Considering their biological profile, an inverse virtual screening approach was employed to identify and suggest putative anticancer interacting targets.
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Irisin Serum Levels in Metabolic Syndrome Patients Treated with Three Different Diets: A Post-Hoc Analysis from a Randomized Controlled Clinical Trial.
Osella, AR, Colaianni, G, Correale, M, Pesole, PL, Bruno, I, Buongiorno, C, Deflorio, V, Leone, CM, Colucci, SC, Grano, M, et al
Nutrients. 2018;(7)
Abstract
BACKGROUND Irisin, a hormone-like myokine, regulates energy homeostasis and mediates the benefits of physical activity on health. METHODS To estimate the effect of different diets on irisin concentrations in subjects with the Metabolic Syndrome (MetS). METHODS Subjects with MetS were derived from a population survey; 163 subjects were enrolled and randomized to a: Low Glycaemic Index (LGID), Mediterranean (MD) or Low Glycaemic Index Mediterranean (LGIMD) Diet, and the groups were compared, also with 80 controls without MetS. Sociodemographic, medical and nutritional data were collected and fasting blood samples drawn. Subjects underwent LUS and bioimpedentiometry. Generalized Estimating Equations were performed. RESULTS At baseline, lower irisin concentrations were observed in MetS subjects. Mean irisin levels increased in all diet groups but only the LGID group reached statistical significance, as well as showing an interaction between LGID and time at the sixth month examination (4.57, 95% CI −1.27, 7.87). There was a positive effect of Vegetable Proteins (0.03, 95% CI −0.01,0.06) and Saturated Fatty Acids (0.04, 95% CI 0.01, 0.07) on irisin concentrations. In the LGIMD, a positive effect on Fat-Free Mass (0.38, 95% CI 0.19, 0.57) and a negative effect on the Body Mass Index (−0.75, 95% CI −1.30, −0.19) were observed. CONCLUSIONS There seems to be a link between diet and muscle physiology. We showed that patients following a LGID had higher levels of irisin, a promising biomarker of muscle activity.
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Clinical usefulness of myocardial innervation imaging using Iodine-123-meta-iodobenzylguanidine scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure: an overview.
Treglia, G, Stefanelli, A, Bruno, I, Giordano, A
European review for medical and pharmacological sciences. 2013;(1):56-68
Abstract
AIM: This study was designed to review published data regarding the clinical usefulness of iodine-123-meta-iodobenzyl-guanidine (MIBG) scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure (HF). METHODS A comprehensive computer literature search of the PubMed/MEDLINE and Embase databases was conducted to find relevant published articles about the clinical usefulness of MIBG scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with HF. RESULTS Thirty-three studies, comprising a total sample size of 1124 patients with HF, were included in this review. Main findings of the included studies are presented. CONCLUSIONS Myocardial innervation imaging using MIBG scintigraphy can be successfully used to assess changes in cardiac sympathetic neuronal function caused by several pharmacological interventions in patients with HF.