Book Review

The intellectual force in this scientifically and technologically oriented century, as Gatland and Dempster indicate, resides with men who have renaissance minds that can ably embrace scientific as well as societal propositions, reason anew and reach unique and far-reaching conclusions beyond the realm of current thought. To date, the intellectual strength of the lawyer has been his pervading understanding of problems from every societal view. This test can remain valid; however, the province of the legal skill-elite group must range far beyond his traditional social science touchstones into decidedly esoteric scientific subjects. The horizon of jurisprudence now embraces the mechanical universe of Newton, the relativistic universe of Einstein, and perhaps even the levels of energy universe of Helmut Hoeppner

Molecular docking simulations on histone deacetylases (Hdac)-1 and-2 to investigate the flavone binding

Histone modifications through acetylation are fundamental for remodelling chromatin and consequently activating gene expression. The imbalance between acetylation and deacetylation activity causes transcriptional dysregulation associated with several disorders. Flavones, small molecules of plant origin, are known to interfere with class I histone deacetylase (HDAC) enzymes and to enhance acetylation, restoring cell homeostasis. To investigate the possible physical interactions of flavones on human HDAC1 and 2, we carried out in silico molecular docking simulations. Our data have revealed how flavone, and other two flavones previously investigated, i.e., apigenin and luteolin, can interact as ligands with HDAC1 and 2 at the active site binding pocket. Regulation of HDAC activity by dietary flavones could have important implications in developing epigenetic therapy to regulate the cell gene expression

Mid-Term Outcome of Mitral Valve Repair and Coronary Artery Bypass Grafting for Ischemic or Degenerative Mitral Regurgitation

Aim of the study. To verify the impact of the etiology of mitral valve regurgitation on a 5-year outcome after repair and concomitant coronary artery bypass grafting (CABG). Methods. One hundred and eleven consecutive patients (mean age of 69±8 years) who underwent mitral valve repair, 65 for ischemic and 46 for degenerative mitral regurgitation, and concomitant CABG, were retrospectively analyzed. The mean follow-up was 40±28 (9-104) months. Five-year survival (including operative mortality), and survival free from events (postoperative low output syndrome, progression of mitral regurgitation, onset or worsening of congestive heart failure, recurrence of myocardial infarction, and the need for mitral valve replacement) were analyzed. Results. Compared with degenerative, ischemic mitral regurgitation was associated with a higher incidence of previous myocardial infarction (P<0.0001), left ventricular ejection fraction (LVEF) <0.45 (P<0.0001), and more diseased coronary vessels per patient (P<0.0001). Five-year all-cause mortality was 18% (20/111). Independent predictors of mortality were older age at operation (P=0.0008), LVEF<0.45 (P=0.04), and the ischemic etiology of mitral regurgitation (P=0.03). At five years, survival was 69%±7.6% for ischemic versus 87%±6.5% for degenerative etiology (P=0.03); event-free survival was 58%±8.4% versus 75%±8% (P=0.02), and freedom from late cardiac death was 85%±6.6% versus 100% (P=0.02). Freedom from mitral valve reoperation was 97±2.4%. Conclusions. Ischemic mitral regurgitation “per se” predicted limited survival and event-free survival. Left ventricular dysfunction is frequently associated with the ischemic etiology. An early surgical indication to prevent left ventricular dysfunction could be important to improve the mid-term outcom

Perspective: Cancer Patient Management Challenges During the COVID-19 Pandemic

On March 11, 2020, the WHO has declared the coronavirus disease 2019 (COVID-19) a global pandemic. As the last few months have profoundly changed the delivery of health care in the world, we should recognize the effort of numerous comprehensive cancer centers to share experiences and knowledge to develop best practices to care for oncological patients during the COVID-19 pandemic. Patients as well as physicians must be aware of all these constraints and profound social, personal, and medical challenges posed by the tackling of this deadly disease in everyday life in order to adjust to such a completely novel scenario. This review will discuss facing the challenges and the current approaches that cancer centers in Italy and United States are adopting in order to cope with clinical and research activities

Thrombosis of the left anterior descending artery due to compression from giant pseudoaneurysm late after a bentall operation.

BACKGROUND: A postoperative pseudoaneurysm may develop and gradually expand in the mediastinal space even late following Bentall operation for aortic root replacement, particularly in patients with dissection of the aorta. METHODS: A very large (148 mm) pseudoaneurysm originating of the right coronary ostium suture line was observed in a patient admitted with unstable angina 6 years after Bentall procedure for type A aortic dissection. Angiograms showed reduced flow in the right coronary and thrombotic subocclusion of the left anterior descending (LAD) coronary artery due to extrinsic compression from the expanding mediastinal mass. RESULTS: Reoperation was performed during femoro-femoral cardiopulmonary bypass and brief period of circulatory arrest to clamp the tubular graft. After closure of the detected right coronary ostium in the tubular graft double bypass, grafting to the right coronary and LAD arteries was required. Postoperative course was uneventful. CONCLUSIONS: Close long-term follow-up after a Bentall procedure is required to minimize the risk of developing a large pseudoaneurysmal mass, in particular, after dissection of the aorta

Kaempferol, myricetin and fisetin in prostate and bladder cancer: A systematic review of the literature

Prostate and bladder cancer represent the two most frequently diagnosed genito-urinary malignancies. Diet has been implicated in both prostate and bladder cancer. Given their prolonged latency and high prevalence rates, both prostate and bladder cancer represent attractive candidates for dietary preventive measures, including the use of nutritional supplements. Flavonols, a class of flavonoids, are commonly found in fruit and vegetables and are known for their protective effect against diabetes and cardiovascular diseases. Furthermore, a higher dietary intake of flavonols was associated with a lower risk of both bladder and prostate cancer in epidemiological studies. In this systematic review, we gathered all available evidence supporting the anti-cancer potential of selected flavonols (kaempferol, fisetin and myricetin) against bladder and prostate cancer. A total of 21, 15 and 7 pre-clinical articles on bladder or prostate cancer reporting on kaempferol, fisetin and myricetin, respectively, were found, while more limited evidence was available from animal models and epidemiological studies or clinical trials. In conclusion, the available evidence supports the potential use of these flavonols in prostate and bladder cancer, with a low expected toxicity, thus providing the rationale for clinical trials that explore dosing, settings for clinical use as well as their use in combination with other pharmacological and non-pharmacological interventions

Gender minorities in breast cancer – Clinical trials enrollment disparities: Focus on male, transgender and gender diverse patients

Background: The last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials. Methods: We conducted a scoping review of phase III clinical trials of agents with a current positioning within the therapeutic algorithms of BC. Results: We selected 51 phase III trials. Men enrollment was allowed in 35.3% of trials. In none of the trial inclusion/exclusion criteria referred to transgender/gender-diverse people. A numerical higher rate of enrolled men was observed in the contemporary as compared to historical group. We found a statistically significant association between the drug class and the possibility of including men: 100%, 80%, 50%, 33.3%, 25%, 10% and 9.1% of trials testing ICI/PARP-i, ADCs, PI3K/AKT/mTOR-i, anti-HER2 therapy, CDK4/6-i, ET alone, and CT alone. Overall, 77409 patients were enrolled, including 112 men (0.2%). None of the trial reported transgender/gender-diverse people proportion. Studies investigating PARP-i were significantly associated with the highest rate of enrolled men (1.42%), while the lowest rates were observed for trials of CT (0.13%), ET alone (0.10%), and CDK 4/6-I (0.08%), p < 0.001. Conclusions: We confirmed that gender minorities are severely underrepresented among BC registration trials. We observed a lower rate of men in trials envisaging endocrine manipulation or in less contemporary trials. This work sought to urge the scientific community to increase the awareness level towards the issue of gender minorities and to endorse more inclusive criteria in clinical trials