Measurement of the Positive Muon Anomalous Magnetic Moment to 0.20 ppm.

We present a new measurement of the positive muon magnetic anomaly, a_{µ}≡(g_{µ}-2)/2, from the Fermilab Muon g-2 Experiment using data collected in 2019 and 2020. We have analyzed more than 4 times the number of positrons from muon decay than in our previous result from 2018 data. The systematic error is reduced by more than a factor of 2 due to better running conditions, a more stable beam, and improved knowledge of the magnetic field weighted by the muon distribution, ω[over ˜]_{p}^{'}, and of the anomalous precession frequency corrected for beam dynamics effects, ω_{a}. From the ratio ω_{a}/ω[over ˜]_{p}^{'}, together with precisely determined external parameters, we determine a_{µ}=116 592 057(25)×10^{-11} (0.21 ppm). Combining this result with our previous result from the 2018 data, we obtain a_{µ}(FNAL)=116 592 055(24)×10^{-11} (0.20 ppm). The new experimental world average is a_{µ}(exp)=116 592 059(22)×10^{-11} (0.19 ppm), which represents a factor of 2 improvement in precision.

Estimating the Impact of Workplace Bullying: Humanistic and Economic Burden among Workers with Chronic Medical Conditions.

BACKGROUND: Although the prevalence of work-limiting diseases is increasing, the interplay between occupational exposures and chronic medical conditions remains largely uncharacterized. Research has shown the detrimental effects of workplace bullying but very little is known about the humanistic and productivity cost in victims with chronic illnesses. We sought to assess work productivity losses and health disutility associated with bullying among subjects with chronic medical conditions. METHODS: Participants (N = 1717) with chronic diseases answered a self-administered survey including sociodemographic and clinical data, workplace bullying experience, the SF-12 questionnaire, and the Work Productivity Activity Impairment questionnaire. RESULTS: The prevalence of significant impairment was higher among victims of workplace bullying as compared to nonvictims (SF-12 PCS: 55.5% versus 67.9%, p < 0.01; SF-12 MCS: 59.4% versus 74.3%, p < 0.01). The adjusted marginal overall productivity cost of workplace bullying ranged from 13.9% to 17.4%, corresponding to Italian Purchase Power Parity (PPP) 2010 US$ 4182-5236 yearly. Association estimates were independent and not moderated by concurrent medical conditions. CONCLUSIONS: Our findings demonstrate that the burden on workers' quality of life and productivity associated with workplace bullying is substantial. This study provides key data to inform policy-making and prioritize occupational health interventions.

The use of first generation versus second generation antipsychotics as add-on or as switch treatment and its effect on QTC interval: the Italian experience in a real-world setting.

Some psychotropic drugs are connected with prolongation of the QT interval, torsade de pointes and sudden death. Recent data suggest that with regard to this adverse effect, the atypical antipsychotic drugs are no safer than the older drugs. The purpose of this study is to evaluate the different use of first generation versus second generation antipsychotics as add-on (Group I) or switch treatment (Group II) and its effect on QTc interval in a sample of schizophrenic and bipolar inpatients without medical illness. All patients had been evaluated twice by using ECG: on admission and after two weeks of hospitalization. Exclusions criteria were: abnormalities in levels of potassium, magnesium and calcium, cardiovascular and metabolic diseases, alcohol or drug abuse. We found a significant (p < 0.01) greater use of first generation antipsychotic in Group I (73.80%) than in the Group II (33.33%). Also Group I showed a significant increase (p < 0.0001) in total chlorpromazine equivalent (476. 78 ± 448.80 mg/day vs 845.48 ± 491.64 mg/day) and in QTc interval (369.14 ± 33.75 ms vs 387.09 ± 31.97 ms), while we did not find any statistical difference in Group II during hospitalization. Our results, in spite of the small sample size, indicate that antipsychotic add-on can increase QTc interval more than switching to other antipsychotic in psychiatric patients without other risk factors.

Intermittent warm blood cardioplegia induces the expression of heat shock protein-72 by ischemic myocardial preconditioning.

OBJECTIVE: Recent studies have demonstrated that the induction of heat shock protein-72 (HSP72) by different stimuli preserves the heart function after cardioplegic arrest. Based on these findings, we investigated whether intermittent warm blood cardioplegia would induce changes in the myocardial expression of HSP72. METHODS: Forty patients scheduled for aortocoronary bypass were randomly assigned to receive either cold or warm intermittent blood cardioplegia. In all patients HSP72 and HSP72 mRNA were assayed in biopsies from the right atrium at baseline, and during the reperfusion period. Plasma CK-MB and troponin-T, and myocardial oxygen extraction and lactate release were also measured. RESULTS: In both groups, myocardial expression of HSP72 increased throughout the reperfusion period, but the values of HSP72 band lengths were significantly higher in the warm group. Correspondingly, HSP72 mRNA levels increased progressively in both groups, with significant difference between groups observed in biopsies at the reperfusion. Warm blood cardioplegia was associated with lower levels of CK-MB and troponin-T. Myocardial oxygen extraction and lactate release were higher during intermittent warm cardioplegia, indicating a more profound ischemic anaerobic metabolism in the warm group. CONCLUSIONS: Intermittent warm blood cardioplegia induces an increased expression of HSP72 and it is associated with a better myocardial protection, by a mechanism involving a variant of the classical ischemic preconditioning model.

Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass.

OBJECTIVE: To investigate the effects of preoperative simvastatin treatment on leucocyte-endothelial interactions following coronary artery bypass surgery with cardiopulmonary bypass. DESIGN: Double blind crossover study. Experiments on polymorphonuclear cells (neutrophils) were done at the end of cardiopulmonary bypass and one hour postoperatively. Endothelial P-selectin expression and neutrophil/endothelial adhesion were evaluated under either normoxic or hypoxic conditions. SETTING: University hospital (tertiary referral centre). PATIENTS: Three groups of patients undergoing coronary bypass surgery: 20 patients taking simvastatin for cholesterol control, 16 patients not responsive to simvastatin, and 20 controls. MAIN OUTCOME MEASURES: Expression of neutrophil CD11b and endothelial P-selectin; adhesion of neutrophils to endothelium. RESULTS: Cardiopulmonary bypass resulted in a significant increase in neutrophil CD11b expression in all groups. Similarly, the exposure of saphenous vein to hypoxia/reoxygenation induced an augmentation of endothelial P-selectin. However, both neutrophil CD11b expression and endothelial P-selectin exocytosis were less in the simvastatin groups than in the controls. Cardiopulmonary bypass and controlled hypoxia/reoxygenation stimulated neutrophil/endothelial adhesion, but the number of adhering cells was less in the simvastatin groups than in the controls, irrespective of the cholesterol concentration. Treatment of endothelial cells with L-NAME completely reversed the effects of simvastatin. CONCLUSIONS: Pretreatment with simvastatin reduces neutrophil adhesion to the venous endothelium in patients undergoing coronary surgery, irrespective of its efficacy at lowering cholesterol concentration.

Left main coronary artery aneurysm: a case report and review of the literature.

Left main coronary artery aneurysm is an uncommon feature of coronary artery disease in adults. We describe the case of a large aneurysm in a 58-year-old patient undergoing cardiac catheterization for effort angina and inducible myocardial ischemia. Specific considerations about the underlying causes and therapeutic options are discussed.

[Statins: from hypocholesteremic drugs to antiatherogenic agents]. / Statine: da farmaci ipocolesterolemizzanti ad agenti antiaterogeni.

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) are widely used for the treatment of hypercholesterolemia. They reduce LDL levels more than other lipid-lowering drugs. Moreover, they are effective in raising HDL and even in reducing triglyceride levels. Statins have an excellent tolerability and safety. Clinical trials in patients with and without ischemic heart disease and with and without high cholesterol levels have demonstrated that statins significantly reduce the relative risk of major coronary events and of total mortality. Other mechanisms independent of LDL lowering may play an important role in the clinical benefits conferred by these drugs and may broaden their therapeutic indications from lipid-lowering to antiatherogenic agents.

Apoptosis in recent myocardial infarction.

PURPOSE: Apoptosis is considered a common pathological feature in acute myocardial infarction (MI) and heart failure; however its role in the later phases post MI has not been characterized. The goal of our study was to investigate by pathological examination human hearts at 20 to 30 days post MI and identify signs of ongoing cell apoptosis. MATERIALS AND METHODS: Two hearts were collected at autopsy from patients who died 20 to 30 days from the onset of MI (Cases 1 and 2). Gross anatomy and light microscopy examination of the hearts was performed to define the infarcted area and the infarct-related artery. The in situ end-labeling of DNA fragmentation (TUNEL) was performed to identify apoptotic cells and the apoptotic rate (AR) was calculated. RESULTS: There were no signs of acute necrosis in any of the specimens examined. A high number of myocardiocyte were positive at TUNEL examination in specimens obtained at sites of infarction, mean AR = 44%, but not in specimens derived from the same patients at regions remote from the MI, AR = 0. CONCLUSIONS: High grade apoptosis is present at sites of infarction and not in regions remote from the infarcted area in the later phases post MI. These data support persistent myocardiocyte loss and identify a possible explanation of progressive left ventricular dysfunction in the subacute phases of MI.

[Platelet glycoprotein IIB-IIIA receptor inhibitors in patients with ischemic heart disease]. / Gli inibitori dei recettori glicoproteici IIB-IIIA delle piastrine nei pazienti con cardiopatia ischemica.

Glycoprotein IIb-IIIa receptor inhibitors are the newest anti-platelets drugs currently used in patients with coronary artery disease. We examined mechanisms of their action and different pharmacokinetic and pharmacodynamic characteristics of the four glycoprotein IIb-IIIa antagonists evaluated in randomized, controlled and multicenter trials. We reviewed results of these trials in the settings of percutaneous revascularizations procedures or unstable coronary syndromes. Platelet glycoprotein IIb-IIIa receptor inhibitors reduced incidence of cardiac death and myocardial infarction during the short- and midterm, and benefit was greater in: a) patients undergoing coronary angioplasty with or without stent implantation, particularly in the presence of unstable angina, diabetes or complex and diffuse coronary artery disease; b) as a direct therapy of unstable coronary syndromes, particularly in patients with refractory angina, diabetes and elevated Troponin; more recently they have been used as adjuvant therapy in acute myocardial infarction. Infusion of these drugs was not associated with higher rates of major bleedings.

Early and long-term results of stenting of diffuse coronary artery disease.

Diffuse coronary artery disease (CAD) is considered unfavorable for interventional procedures; however, the results of stenting of diffuse CAD have not been completely characterized. We performed stenting in 100 consecutive patients with diffuse CAD, defined as significant stenosis >20 mm (n = 59 patients), multiple significant stenoses in the same artery (n = 23 patients), or significant narrowing involving the whole length of the coronary artery (n = 18 patients). Angiographic success was achieved in 103 arteries (100%) and clinical success was obtained in all 100 patients. There were no deaths; no patient had stent closure, acute myocardial infarction, or required emergency coronary artery bypass surgery. All 100 patients had >6 months follow-up (mean 18 +/- 7 months, range 7 to 31); 77 (77%) remained asymptomatic, and 5 (5%) had acute myocardial infarction, of whom 2 died (2%). In-stent restenosis was observed in 12 patients (12%) and repeat angioplasty was performed in 10. Including those patients who underwent repeat angioplasty, 89 (89%) maintained clinical improvement and 95 (95%) were alive and free of bypass surgery during follow-up. Life-table analysis showed 86% freedom from death, myocardial infarction, and target lesion revascularization at 28 months. Thus, selected patients with diffuse CAD may be treated with satisfactory acute and long-term results by stent implantation.

Intravascular physiologic evaluation of the left anterior small thoracotomy operation: a novel approach to left anterior descending artery revascularization.

BACKGROUND: Efficacy and long-term patency rate of the left internal mammary artery (LIMA) conduits for revascularization of the left anterior descending coronary artery (LAD) has been demonstrated, with improved results as compared to the saphenous vein graft operation. Novel approaches to LAD revascularization including the use of the left anterior small thoracotomy (LAST) operation with persistence of the intercostal arteries compared to the traditional LIMA operation have not been reported. This study evaluated flow characteristics of LAST operation. METHODS: Phasic blood flow velocity in the proximal and distal arterial conduit segments was measured in 30 patients by intravascular Doppler flow wire after surgical revascularization of the LAD: 15 patients were revascularized by conventional operation using the LIMA (Group A), and 15 patients were submitted to the LAST operation (Group B). All patients underwent coronary angiography and ventriculography at 116 +/- 111 days after operation. Only angiographically normal grafts with normal left ventricular wall motion and coronary arteries free from significant distal stenosis were included for coronary flow velocity and reserve measurements. RESULTS: The diastolic/systolic velocity ratio in the proximal portion of the internal mammary artery was similar in the two groups (Group A 0.8 +/- 0.2 vs Group B 0.7 +/- 0.3, p = NS). Distal diastolic/systolic velocity ratio in Group A (1.7 +/- 0.1) was higher than Group B (0.9 +/- 0.3, p < 0.001). There were no differences in basal average peak velocity or coronary flow reserve between the proximal and distal segments for either groups. CONCLUSIONS: Although proximal phasic coronary flow patterns between the two groups were similar, distal diastolic/systolic velocity ratio was higher in the LIMA than in the LAST. This difference may be related to the persistence of the intercostal artery in the LAST operation. These data confirm the continued patency and similar functional flow patterns compared to the conventional LIMA operation, supporting further investigation and application of this novel approach to LAD revascularization.

Gemcitabine-induced atrial fibrillation: a hitherto unreported manifestation of drug toxicity.

BACKGROUND: Gemcitabine is an antimetabolic drug for solid tumors. Although its pharmacokinetics as well as its side-effects are well known, paroxysmal atrial fibrillation associated to the administration of this drug has not yet been described. PATIENTS AND METHODS: We describe the case of a 78-year-old man with pancreatic adenocarcinoma who presented repeated paroxysmal atrial fibrillation episodes 18-24 hours after every gemcitabine infusion which resolved with antiarrhythmic drugs. This clinical history was positive for a remote brief episode of atrial fibrillation, which resolved spontaneously, and the patient had no predisposing factors for supraventricular arrhythmias (systemic hypertension, diabetes or coronary artery disease). RESULTS: Cardiac work-up revealed only a mild mitral-valve prolapse and complete right bundle branch block. During the arrhythmia episodes no other precipitating factors were reported. The close temporal relationship of the arrhythmia to drug administration and the recurrence of arrhythmia upon rechallenge allowed to hypothesize an intrinsic pro-arrhythmic effect of gemcitabine or its metabolite 2',2'-difluorodeoxyuridine. CONCLUSIONS: The occurrence of atrial fibrillation during the administration of gemcitabine may be considered as a cardiac arrhythmia drug-related toxicity. This side-effect of gemcitabine infusion is a previously unreported sign of drug toxicity; therefore, a high level of awareness to this problem is warranted when this drug is administered.

Vascular and haemostatic gene polymorphisms associated with non-fatal myocardial infarction: a critical review.

The importance of genetics to the pathogenesis of myocardial infarction is suggested by the frequent familial clustering of premature disease. Yet, studies associating myocardial infarction with gene polymorphisms of vascular proteins (angiotensinogen, angiotensin converting enzyme, angiotensin II type 1 receptor, endothelial nitric oxide synthase) and haemostatic factors (fibrinogen, coagulation factors II, V, VII and XIII, plasminogen activator inhibitor-1, tissue-type plasminogen activator, platelet glycoproteins IIb/IIIa, Ia/IIa and Ib-IX-V, or methylenetetrahydrofolate reductase) have revealed conflicting results. This is hardly surprising, given: 1) the multigenic nature of myocardial infarction, whereby single polymorphisms are bound to play at best only a limited role in the global risk of disease; 2) the multiple pathogenetic mechanisms of infarction (e.g., atheromatous obstruction, plaque rupture, thrombosis, vasospasm), each of which is likely influenced by a number of genes and by several environmental factors. The simultaneous investigation of a set of polymorphisms--and of their interactions with environmental factors--in extremely homogeneous sets of patients should offer a better understanding of the contribution of specific genes to the risk of myocardial infarction.

Directional coronary atherectomy: from therapeutic device to research tool in coronary artery disease.

Directional coronary atherectomy (DCA) was introduced as a new percutaneous revascularization modality in 1990, and was initially applied to large vessels without tortuosity or calcification, with overall results including a 95% procedural success, 94% clinical success and 4.6% major complications (urgent bypass surgery in 3.8%, Q wave myocardial infarction in 1.7%, and hospital mortality in 0.3% of patients). In addition to its established efficacy for eccentric lesions, newer applications emerged such as treatment of saphenous vein grafts, thrombus-associated lesions, aorto-ostial lesions, failed or suboptional coronary angioplasty results, bifurcation lesions and use as a part of multi-vessel intervention. Comparative studies with coronary angioplasty such as CAVEAT I and II and CCAT showed better success rates with DCA vs coronary angioplasty, but failed to demonstrate benefit in restenosis rates. OARS and BOAT studies helped define optimal atherectomy techniques, which led to better acute angiographic results and to the "debulking plus stenting" concept. A spin-off of those clinical applications has been the opportunity to study the histology of tissue excised by DCA in vivo in different clinical settings. Such studies, investigating plaque ulceration, thrombosis and inflammation are reviewed, with special emphasis on new insights into unstable angina; the future of atherectomy research is also outlined with a categorization of various possible protocols to be applied utilizing coronary atherectomy specimens from live patients.

[Remodelling of the radial artery graft 5 years after aortocoronary bypass intervention]. / Rimodellamento dei graft in arteria radiale a cinque anni dall'intervento di bypass aortocoronarico.

BACKGROUND: The radial artery (RA) is being employed as coronary artery bypass graft with good results, but when it is proximally anastomosed to the ascending aorta, undergoes substantial hemodynamic changes which could lead to significant graft intimal hyperplasia. The aim of this study was to investigate the evolution of RA graft morphology over time. METHODS: We studied 20 patients with a perfectly patent RA graft at both 1 and 5 year angiography after coronary artery bypass graft. RESULTS: Both RA graft and grafted coronary artery diameters, assessed by quantitative coronary angiography, significantly increased at 5 years, in comparison to 1 year angiography (2.08 +/- 0.45 vs 2.54 +/- 0.53 mm, +22%, p < 0.001 and 1.92 +/- 0.47 vs 2.18 +/- 0.41 mm, +13.3%, p < 0.001, respectively). CONCLUSIONS: Hemodynamic changes following RA employment for coronary artery bypass graft stimulate a remodeling of RA graft itself and of the grafted coronary arteries. The progressive increase of diameters observed in RA grafts strongly argues against the development of flow-limiting graft intimal hyperplasia when RA is proximally anastomosed to the ascending aorta. Moreover, grafted coronary artery dilation suggests that hemorrheologic changes following coronary artery bypass graft could play a major role in the development of RA remodeling over time.

Improvement of myocardial ischemia by subclavian stent implantation in patients with internal mammary grafts: a case report and review of the literature.

In patients with coronary bypass which utilizes left (LIMA) or right internal mammary artery (RIMA), recurrent ischemia is often due to stenosis of the distal anastomoses of the grafts. However, occasionally, ischemia may be due to extracoronary causes, such as subclavian disease proximal to the internal mammary artery origins. This case report describes such clinical situation emphasizing the need for careful patient evaluation, and discusses therapeutic interventional options, in particular, safety and effectiveness of self expanding subclavian stent implantation. A review of the literature is also presented.

Coronary stenting in patients with situs viscerum inversus.

Atherosclerotic coronary disease may develop even in patients with complex cardiovascular anomalies who reach adult life. Coronary revascularization (surgical or interventional) may present potential difficulties related to the unusual anatomy. We describe two cases of situs viscerum inversus who underwent cardiac catheterization and angiography as adults because of ingravescent angina. The study identified the cardiac relations and connections, and diagnosed severe coronary disease that was successfully treated with coronary angioplasty and stent implantation. The implications of performing such procedures in patients with similar cardiac anomalies are discussed.