A novel ultrafast-low-dose computed tomography protocol allows concomitant coronary artery evaluation and lung cancer screening

BACKGROUND:Cardiac computed tomography (CT) is often performed in patients who are at high risk for lung cancer in whom screening is currently recommended. We tested diagnostic ability and radiation exposure of a novel ultra-low-dose CT protocol that allows concomitant coronary artery evaluation and lung screening. METHODS: We studied 30 current or former heavy smoker subjects with suspected or known coronary artery disease who underwent CT assessment of both coronary arteries and thoracic area (Revolution CT, General Electric). A new ultrafast-low-dose single protocol was used for ECG-gated helical acquisition of the heart and the whole chest. A single IV iodine bolus (70-90 ml) was used. All patients with CT evidence of coronary stenosis underwent also invasive coronary angiography. RESULTS: All the coronary segments were assessable in 28/30 (93%) patients. Only 8 coronary segments were not assessable in 2 patients due to motion artefacts (assessability: 98%; 477/485 segments). In the assessable segments, 20/21 significant stenoses (> 70% reduction of vessel diameter) were correctly diagnosed. Pulmonary nodules were detected in 5 patients, thus requiring to schedule follow-up surveillance CT thorax. Effective dose was 1.3 ± 0.9 mSv (range: 0.8-3.2 mSv). Noteworthy, no contrast or radiation dose increment was required with the new protocol as compared to conventional coronary CT protocol. CONCLUSIONS:The novel ultrafast-low-dose CT protocol allows lung cancer screening at time of coronary artery evaluation. The new approach might enhance the cost-effectiveness of coronary CT in heavy smokers with suspected or known coronary artery disease

Glutathione infusion before primary percutaneous coronary intervention: A randomised controlled pilot study

Objective: In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H2O2) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment. Glutathione (GSH) is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesised that the infusion of GSH before acute reoxygenation might counteract the deleterious effects of increased H2O2 generation on myocardium. Methods: Fifty consecutive patients with STEMI, scheduled to undergo primary angioplasty, were randomly assigned, before intervention, to receive an infusion of GSH (2500 mg/25 mL over 10 min), followed by drug administration at the same doses at 24, 48 and 72 hours elapsing time or placebo. Peripheral blood samples were obtained before and at the end of the procedure, as well as after 5 days. H2O2 production, 8-iso-prostaglandin F2α (PGF2α) formation, H2O2 breakdown activity (HBA) and nitric oxide (NO) bioavailability were determined. Serum cardiactroponin T (cTpT) was measured at admission and up to 5 days. Results: Following acute reperfusion, a significant reduction of H2O2 production (p=0.0015) and 8-iso-PGF2α levels (p=0.0003), as well as a significant increase in HBA (p<0.0001)and NO bioavailability (p=0.035), was found in the GSH group as compared with placebo. In treated patients, attenuated production of H2O2 persisted up to 5 days from the index procedure (p=0.009) and these changes was linked to those of the cTpT levels (r=0.41, p=0.023). Conclusion: The prophylactic and prolonged infusion of GSH seems to determine a rapid onset and persistent blunting of H2O2 generation improving myocardial cell survival. Nevertheless, a larger trial, adequately powered for evaluation of clinical endpoints, is ongoing to confirm the current finding

A new software for automated counting of glistenings in intraocular lenses in vivo

AIM: To assess the performance of a bespoke software for automated counting of intraocular lens (IOL) glistenings in slit-lamp images. METHODS: IOL glistenings from slit-lamp-derived digital images were counted manually and automatically by the bespoke software. The images of one randomly selected eye from each of 34 participants were used as a training set to determine the threshold setting that gave the best agreement between manual and automatic grading. A second set of 63 images, selected using randomised stratified sampling from 290 images, were used for software validation. The images were obtained using a previously described protocol. Software-derived automated glistenings counts were compared to manual counts produced by three ophthalmologists. RESULTS: A threshold value of 140 was determined that minimised the total deviation in the number of glistenings for the 34 images in the training set. Using this threshold value, only slight agreement was found between automated software counts and manual expert counts for the validating set of 63 images (κ=0.104, 95%CI, 0.040-0.168). Ten images (15.9%) had glistenings counts that agreed between the software and manual counting. There were 49 images (77.8%) where the software overestimated the number of glistenings. CONCLUSION: The low levels of agreement show between an initial release of software used to automatically count glistenings in in vivo slit-lamp images and manual counting indicates that this is a non-trivial application. Iterative improvement involving a dialogue between software developers and experienced ophthalmologists is required to optimise agreement. The results suggest that validation of software is necessary for studies involving semi-automatic evaluation of glistenings

Enoximone echocardiography: a novel test to evaluate left ventricular contractile reserve in patients with heart failure on chronic beta-blocker therapy

BACKGROUND: It has been suggested that an extensive contractile reserve identified recognised by means of dobutamine stress echocardiography may predict a better prognosis in patients with severe left ventricular dysfunction at rest. However, the clinical use of dobutamine stress echocardiography may be limited in patients with chronic heart failure by the substantial proportion of such patients treated with beta-blockers, since the inotropic response to adrenergic stimulation is known to be attenuated in patients receiving beta-adrenoceptor blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis that enoximone may be an alternative to dobutamine in evaluating left ventricular contractile reserve in patients with systolic dysfunction on chronic beta-blocker therapy. METHODS: We studied 26 patients (21 males and five females) with a mean age of 58 ± 10 years: 11 were not receiving beta-blockers (noBB group); 15 were receiving carvedilol at a mean dose of 34 mg/day (BB group). Dobutamine was infused at doses of 5 and 10 micrograms/kg/min, and enoximone at a dose of 1.5 mg/kg. RESULTS: The ejection fraction in the noBB group increased by 9% with dobutamine and 8.73% with enoximone (p = 0.86); in the BB group, it increased by 6% with dobutamine and 8.94% with enoximone (p = 0.03). Regional peak systolic velocities were evaluated by means of tissue Doppler imaging in four basal and four medium level segments. In the noBB group, they increased more with dobutamine than with enoximone in three of the eight segments; no significant differences were found in the BB group. Dobutamine induced non-sustained ventricular tachycardia in three patients and supraventricular tachycardia in one, whereas enoximone did not induce any repetitive arrhythmias. CONCLUSIONS: Enoximone might be preferable to low-dose dobutamine for evaluating left ventricular contractile reserve in chronically beta-blocked heart failure patients as it is slightly more potent and has a better safety profile

Cardiovascular and hormonal responses to static handgrip in young and older healthy men

The purpose of this study was to investigate the effect of age on cardiovascular changes and plasma concentrations of adrenomedullin (ADM), catecholamines, endothelin-1 (ET-1) and plasma renin activity (PRA) in healthy men. A total of 15 young (21 ± 0.3 years) and 15 older (64 ± 0.7 years) healthy men performed two 3-min bouts of static handgrip at 30% of maximal voluntary contraction, alternately with each hand without any break between the bouts. During exercise heart rate (HR), blood pressure (BP), stroke volume (SV) and pre-ejection period (PEP) and left ventricle ejection time (LVET) were measured. Blood samples were taken before exercise, at the end of both exercise bouts and in the fifth minute of the recovery period. The handgrip-induced increases in HR and cardiac output were significantly smaller in older than in young men (p < 0.01). SV decreased only in older men (p < 0.001). There were no differences between groups in BP increases. The baseline plasma ADM and catecholamines were higher in older man compared to young subjects. Handgrip caused increases in plasma ADM, ET-1 and PRA only in older men (p < 0.05). The increases in plasma ADM correlated positively with those of noradrenaline (NA), PRA, ET-1 and LVET and negatively with changes in total peripheral resistance (TPR), SV, PEP and PEP/LVET ratio. The increases in plasma ET-1 correlated positively with those of NA, PRA, TPR, mean BP and SV. These results revealed that ADM, ET-1 and angiotensin II can contribute to maintain vascular tone during static exercise in older but not in younger men

Vascular endothelial growth factor in children with neuroblastoma: a retrospective analysis

BACKGROUND: Despite aggressive therapy, advanced stage neuroblastoma patients have poor survival rates. Although angiogenesis correlates with advanced tumour stage and plays an important role in determining the tumour response to treatment in general, clinical data are still insufficient, and more clinical evaluations are needed to draw conclusions. The aim of this study was to evaluate vascular endothelial growth factor (VEGF) expression in patients with neuroblastoma, determine whether it correlates with other prognostic factors and/or therapeutic response, and to assess should VEGF be considered in a routine diagnostic workup. ----- MATERIALS AND METHODS: VEGF expression was determined by immunohistochemistry using anti-VEGF antibody in paraffin embedded primary tumour tissue from 56 neuroblastoma patients. Semiquantitative expression of VEGF was estimated and compared with gender, age, histology, disease stage, therapy, and survival. Statistical analyses, including multivariate analysis, were performed. ----- RESULTS: VEGF expression correlated with disease stage and survival in neuroblastoma patients. Combination of VEGF expression and disease stage as a single prognostic value for survival (P-value = 0.0034; odds ratio (OR) (95%CI) = 26.17 (2.97-230.27) exhibited greater correlation with survival than individually. Hematopoietic stem cell transplantation significantly improved survival of the advanced stage patients with high VEGF expression. ----- CONCLUSION: VEGF expression should be considered in a routine diagnostic workup of children with neuroblastoma, especially in those more than 18 months old and with advanced disease stage. High VEGF expression at the time of disease diagnosis is a bad risk prognostic factor, and can be used to characterize subsets of patients with an unfavourable outcome

Sex and Gender Differences in Ischemic Heart Disease: Endocrine Vascular Disease Approach (EVA) Study Design

Improvements in ischemic heart disease (IHD) management have been unbalanced between sexes, with coronary microvascular dysfunction considered the likely underlying reason. The Endocrine Vascular disease Approach (EVA) is an observational study (Clinicaltrial.gov NCT02737982) aiming to assess sex and gender interactions between coronary circulation, sexual hormones, and platelet function. Consecutive patients with IHD undergoing coronary angiography will be recruited: (1) to assess sex and gender differences in angiographic reperfusion indexes; (2) to evaluate the effects of estrogen/androgen on sex-related differences in myocardial ischemia; (3) to investigate the platelet biology differences between men and women with IHD; (4) to verify sex- and gender-driven interplay between response to percutaneous coronary intervention, platelets, sex hormones, and myocardial damage at baseline and its impact on 12-month outcomes. The integration of sex and gender in this translational project on IHD will contribute to the identification of new targets for further innovative clinical interventions

The Efficacy of Tetracyclines in Peripheral and Intracerebral Prion Infection

We have previously shown that tetracyclines interact with and reverse the protease resistance of pathological prion protein extracted from scrapie-infected animals and patients with all forms of Creutzfeldt-Jakob disease, lowering the prion titre and prolonging survival of cerebrally infected animals. To investigate the effectiveness of these drugs as anti-prion agents Syrian hamsters were inoculated intramuscularly or subcutaneously with 263K scrapie strain at a 10−4 dilution. Tetracyclines were injected intramuscularly or intraperitoneally at the dose of 10 mg/kg. A single intramuscular dose of doxycycline one hour after infection in the same site of inoculation prolonged median survival by 64%. Intraperitoneal doses of tetracyclines every two days for 40 or 44 days increased survival time by 25% (doxycycline), 32% (tetracycline); and 81% (minocycline) after intramuscular infection, and 35% (doxycycline) after subcutaneous infection. To extend the therapeutic potential of tetracyclines, we investigated the efficacy of direct infusion of tetracyclines in advanced infection. Since intracerebroventricular infusion of tetracycline solutions can cause overt acute toxicity in animals, we entrapped the drugs in liposomes. Animals were inoculated intracerebrally with a 10−4 dilution of the 263K scrapie strain. A single intracerebroventricular infusion of 25 µg/ 20 µl of doxycycline or minocycline entrapped in liposomes was administered 60 days after inoculation, when 50% of animals showed initial symptoms of the disease. Median survival increased of 8.1% with doxycycline and 10% with minocycline. These data suggest that tetracyclines might have therapeutic potential for humans

Transcatheter Aortic Valve Replacement in Pure Native Aortic Valve Regurgitation

Cardiolog