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

Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer

Background: Mutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC). However, it is not yet clear whether specific TP53 mutations bear distinct clinical and pathophysiological significance in different HNSCC subgroups. Methods: A systematic bioinformatics appraisal of TP53 mutations was performed on 415 HNSCC cases available on The Cancer Genome Atlas (TCGA). The following features were analysed and correlated with known clinicopathological variables: mutational profile of TP53, location (within secondary structure and predicted domains of p53 protein) and well-known hotspot mutations. Interactome–genome–transcriptome network analysis highlighted different gene networks. An algorithm was generated to develop a new prognostic classification system based on patients’ overall survival. Results: TP53 mutations in HNSCCs exhibited distinct differences in different anatomical sites. The mutational profile of TP53 was an independent prognostic factor in HNSCC. High risk of death mutations, identified by our novel classification algorithm, was an independent prognostic factor in TCGA HNSCC database. Finally, network analysis suggested that distinct p53 molecular pathways exist in a site- and mutation-specific manner. Conclusions: The mutational profile of TP53 may serve as an independent prognostic factor in HNSCC patients, and is associated with distinctive site-specific biological networks

Long Stent Implantation on the Left Anterior Descending Coronary Artery at a Follow-Up of More Than Five Years

Background: Stent implantation represents the standard of care in coronary intervention. While a short stent implanted on a focal lesion located on the left anterior descending artery (LAD) seems a reasonable alternative to an internal mammary implant, the same for long stents is still debated. Methods: We reported the long-term data of 531 consecutive patients who underwent Percutaneous Coronary Intervention (PCI) with long stents in two highly specialized centres. The main inclusion criteria were the implantation of stents longer than 30 mm on the LAD and a minimum follow-up (FU) of five years. The primary endpoint was mortality, and the secondary endpoints were any myocardial infarction (MI), target vessel and lesion revascularization (TVR and TLR, respectively), and stent thrombosis (ST) observed as definite, probable, or possible. Results: In this selected population with characteristics of complex PCI (99.1%), the long-term follow-up (mean 92.18 ± 35.5 months) estimates of all-cause death, cardiovascular death, and any myocardial infarction were 18.3%, 10.5%, and 9.3%, respectively. Both all-cause and cardiovascular deaths are significantly associated with three-vessel disease (HR 6.8; confidence of interval (CI) 95% 3.844–11.934; p &lt; 0.001, and HR 4.7; CI 95% 2.265–9.835; p &lt; 0.001, respectively). Target lesion (TLR) and target vessel revascularization (TVR) are associated with the presence of three-lesion disease on the LAD (HR 3.4; CI 95% 1.984–5.781; p &lt; 0.001; HR 3.9 CI 95% 2.323–6.442; p &lt; 0.001, respectively). Re-PCI for any cause occurred in 31.5% of patients and shows an increased risk for three-lesion stenting (HR 4.3; CI 95% 2.873–6.376; p &lt; 0.001) and the treatment of bifurcation with two stents (HR 1.6; 95% CI 1.051–2.414; p = 0.028). Stent thrombosis rate at the 5-year FU was 4.4% (1.3% definite; 0.9% probable; 2.1% possible), including a 1.7% rate of very-late thrombosis. The stent length superior to 40 mm was not associated with poor outcomes (all-cause death p = 0.349; cardiovascular death p = 0.855; MI p = 0.691; re-PCI p = 0.234; TLR p = 0.805; TVR p = 0.087; ST p = 0.189). Conclusion: At an FU of longer than five years, patients treated with stents longer than 30 mm in their LAD showed acceptable procedural results but poor outcomes.</p

Long Stent Implantation on the Left Anterior Descending Coronary Artery at a Follow-Up of More Than Five Years

Background: Stent implantation represents the standard of care in coronary intervention. While a short stent implanted on a focal lesion located on the left anterior descending artery (LAD) seems a reasonable alternative to an internal mammary implant, the same for long stents is still debated. Methods: We reported the long-term data of 531 consecutive patients who underwent Percutaneous Coronary Intervention (PCI) with long stents in two highly specialized centres. The main inclusion criteria were the implantation of stents longer than 30 mm on the LAD and a minimum follow-up (FU) of five years. The primary endpoint was mortality, and the secondary endpoints were any myocardial infarction (MI), target vessel and lesion revascularization (TVR and TLR, respectively), and stent thrombosis (ST) observed as definite, probable, or possible. Results: In this selected population with characteristics of complex PCI (99.1%), the long-term follow-up (mean 92.18 ± 35.5 months) estimates of all-cause death, cardiovascular death, and any myocardial infarction were 18.3%, 10.5%, and 9.3%, respectively. Both all-cause and cardiovascular deaths are significantly associated with three-vessel disease (HR 6.8; confidence of interval (CI) 95% 3.844–11.934; p &lt; 0.001, and HR 4.7; CI 95% 2.265–9.835; p &lt; 0.001, respectively). Target lesion (TLR) and target vessel revascularization (TVR) are associated with the presence of three-lesion disease on the LAD (HR 3.4; CI 95% 1.984–5.781; p &lt; 0.001; HR 3.9 CI 95% 2.323–6.442; p &lt; 0.001, respectively). Re-PCI for any cause occurred in 31.5% of patients and shows an increased risk for three-lesion stenting (HR 4.3; CI 95% 2.873–6.376; p &lt; 0.001) and the treatment of bifurcation with two stents (HR 1.6; 95% CI 1.051–2.414; p = 0.028). Stent thrombosis rate at the 5-year FU was 4.4% (1.3% definite; 0.9% probable; 2.1% possible), including a 1.7% rate of very-late thrombosis. The stent length superior to 40 mm was not associated with poor outcomes (all-cause death p = 0.349; cardiovascular death p = 0.855; MI p = 0.691; re-PCI p = 0.234; TLR p = 0.805; TVR p = 0.087; ST p = 0.189). Conclusion: At an FU of longer than five years, patients treated with stents longer than 30 mm in their LAD showed acceptable procedural results but poor outcomes.</p

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

Transapical mitral valve implantation for treatment of symptomatic mitral valve disease: a real-world multicentre experience.

AIMS Transcatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real-world data have not yet been reported. This study aimed to assess procedural and 30-day outcomes of TMVI in a real-world patient cohort. METHOD AND RESULTS All consecutive patients undergoing implantation of a transapically delivered self-expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry. Among 108 surgical high-risk patients included (43% female, mean age 75 ± 7 years, mean STS-PROM 7.2 ± 5.3%), 25% was treated for an off-label indication (e.g. previous MV intervention or surgery, mitral stenosis, mitral annular calcification). Patients were highly symptomatic (New York Heart Association [NYHA] functional class III/IV in 86%) and mitral regurgitation (MR) was graded 3+/4+ in 95% (38% primary, 37% secondary, and 25% mixed aetiology). Technical success rate was 96%, and MR reduction to ≤1+ was achieved in all patients with successful implantation. There were two procedural deaths and 30-day all-cause mortality was 12%. At early clinical follow-up, MR reduction was sustained and there were significant reductions of pulmonary pressure (systolic pulmonary artery pressure 52 vs. 42 mmHg, p < 0.001), and tricuspid regurgitation severity (p = 0.013). Heart failure symptoms improved significantly (73% in NYHA class I/II, p < 0.001). Procedural success rate according to MVARC criteria was 80% and was not different in patients treated for an off-label indication (74% vs. 81% for off- vs. on-label, p = 0.41). CONCLUSION In a real-world patient population, TMVI has a high technical and procedural success rate with efficient and durable MR reduction and symptomatic improvement