Does additional coronary artery bypass grafting to aortic valve replacement in elderly patients affect the early and long-term outcome?

Early and long-term outcomes in elderly patients who underwent isolated aortic valve replacement (iAVR) are well defined. Conflicting data exist in elderly patients who underwent AVR plus coronary artery bypass grafting (CABG). We sought to evaluate the early and long-term outcomes of combined AVR + CABG in patients older than 75 years of age. From June 1999 to June 2018, 402 patients ≥ 75 years who underwent iAVR (n = 200; 49.7%) or combined AVR plus CABG (n = 202; 50.3%) were retrospectively analysed. AVR + CABG patients were older than iAVR patients (78.5 ± 2.5 vs 77.6 ± 2.8 years; p < 0.0001), with greater co-morbidities and more urgent/emergency surgery. 30-day mortality was 6.5% in the AVR + CABG and 4.5% in the iAVR group (p = 0.38). Multivariate analysis identified EuroSCORE II [odd ratio (OR) 1.13] postoperative stroke (OR 12.53), postoperative low cardiac output syndrome (OR 8.72) and postoperative mechanical ventilation > 48 h (OR 8.92) as independent predictors of 30-day mortality; preoperative cerebrovascular events (OR 3.43), creatinine (OR 7.27) and extracorporeal circulation time (OR 1.01) were independent predictors of in-hospital major adverse cardiovascular and cerebral events (MACCE). Treatment was not an independent predictor of 30-day mortality and in-hospital MACCE. Survival at 1, 5 and 10 years was 94.7 ± 1.6%, 72.6 ± 3.6% and 31.7 ± 4.8% for iAVR patients and 89.1 ± 2.3%, 73.9 ± 3.5% and 37.2 ± 4.8% for AVR + CABG subjects (p = 0.99). Using adjusted Cox regression model, creatinine [hazard ration (HR) 1.50; p = 0.018], COPD (HR 1.97; p = 0.003) and NYHA class (HR 1.39; p < 0.0001) were independent predictors of late mortality; the combined AVR + CABG was not associated with increased risk of late mortality (HR 0.83; p = 0.30). In patients aged ≥ 75 years, combined AVR + CABG was not associated with increased 30-day mortality, in-hospital MACCE and long-term mortality. Surgical revascularization can be safely undertaken at the time of AVR in elderly patients.

Postinfarction left ventricular free wall rupture: a 17-year single-centre experience.

OBJECTIVES: Left ventricular free wall rupture (LVFWR) is a catastrophic complication following acute myocardial infarction with an estimated incidence of 0.2-7.6% and mortality can be as high as 60%. This study aimed to identify the risk factors for morbidity and mortality in patients affected by LVFWR. METHODS: This is a retrospective study of 35 patients who underwent surgery for LVFWR between January 2000 and December 2016 at our institution. RESULTS: The mean age of patients was 68.3 years. The in-hospital survival was 65.7% (n = 23), and 13% of survived patients presented with cardiac arrest. The following characteristics were associated with in-hospital mortality at univariable analysis: pre-existing hypertension (P = 0.02), need for inotropes (P = 0.02) and cardiac arrest (P < 0.0001) at presentation, cardiopulmonary resuscitation (P = 0.004), preoperative extracorporeal membrane oxygenation (P = 0.004), technique of LVFWR repair (P = 0.013), operation on extracorporeal membrane oxygenation (P = 0.005) and postoperative extracorporeal membrane oxygenation (P = 0.001). In the multivariable analysis, cardiac arrest at presentation was an independent predictor of in-hospital mortality (odds ratio 11.7, 95% confidence interval 2.352-59.063; P = 0.003). The overall mean postoperative follow-up was 8.3 ± 1.3 years. Overall survival rates at 5 and 10 years were 53.2 ± 8.6% and 49.1 ± 8.9%, respectively. Among the survivors, only 6 (26.1%) patients died during follow-up with a 5-year and 10-year overall survival rate of 80.9 ± 8.7% and 74.7 ± 10%, respectively. CONCLUSIONS: These data suggest a trend towards long-term benefit in patients surviving high-risk surgery for LVFWR repair. Considering the high lethality of LVFWR, the urgency and complexity of the primary surgical intervention early diagnosis and prompt surgery play a key role in the management of this complication.

Incidence of perioperative stroke in clampless aortic anastomosis during off-pump coronary artery bypass grafting.

This study aimed to assess if clampless off-pump coronary artery bypass grafting (OPCAB) decreases the incidence of perioperative stroke (POS) rate and in-hospital mortality. The secondary aim was to evaluate 12-year rates of overall mortality. Between January 2003 to December 2015, data of 645 consecutive patients undergoing isolated CABG were retrospectively collected. 363 underwent aortic no-touch OPCAB (No-touch group) and 282 underwent OPCAB with the Heartstring device (HS group). In-hospital mortality and perioperative stroke rate as primary endpoint, as well as long-term follow-up outcome were analysed. In-hospital mortality was lower into No-touch group compared with HS group but without significant statistical difference (1.7 vs. 3.2%, p = 0.19, respectively); the rate of postoperative stroke was higher in No-touch group compared with HS group, although this difference did not reach statistically significance. Delirium was reported with higher presentation rate in HS group (3.9 vs. 0.8%, p = 0.01). Blood transfusions rate was higher in HS subjects (23.4 vs. 16.1%, p = 0.01). Intubation time, ICU, and hospital length of stay were increased in the HS group (p = 0.008, p = 0.001 and p = 0.003, respectively). Over a 12-year follow-up period, survival probabilities at 1, 5, and 10 years were 93.6 ± 1.3 vs. 93.2 ± 1.5, 80.4 ± 2.6 vs. 80.3 ± 2.2, and 57.9 ± 5 vs. 58.4 ± 3.8% in the No-touch and HS group, respectively (p = 0.97). In this retrospective study, clampless off-pump CABG lowers perioperative stroke rate whose incidence is, however, not inferior compared with No-touch technique, and no statistically significance was detected. Delirium has a higher presentation rate in clampless off-pump CABG.

Implantation of the Jarvik 2000® left ventricular assist device using the miniaturized extracorporeal circulation system - a case report.

Myocardial failure is generally considered to be a progressive, irreversible medical condition with characteristic ventricular enlargement, spatial alteration of the heart chambers, diminished cardiac inotropy and resultant dysfunctional, mechanically inefficient heart.The Jarvik 2000®, similar to the mechanical pump, is an electrically powered, axial-flow left ventricular assist device (LVAD) designed to enhance the function of the chronically failing heart and, consequently, normalize the cardiac output for a long period of time.We report the case of 70-year-old man with congestive dilated cardiomyopathy and bioprosthetic mitral valve who underwent surgical implantation of the Jarvik 2000® LVAD, using the miniaturized extracorporeal circulation (MECC) system.The LVAD was implanted through a left thoracotomy and the MECC system was used to avoid intraoperative spontaneous hemodynamic instability and/or malignant ventricular arrhythmia. The circulatory support with the MECC system was optimal and no complication in terms of hemodynamic instability and perioperative bleeding was recorded. The MECC system obliterated the adverse effects associated with conventional extracorporeal circulation, which are often fatal in critically-ill patients.

Post-valvular surgery multi-vessel coronary artery spasm - A literature review.

Coronary artery spasm (CAS) refers to the spontaneous or stimuli-induced transient, often localized and intense subtotal or total constriction/occlusion of the epicardial coronary artery, usually concomitant with angina pectoris with associated elevation of the ST segment on electrocardiogram (ECG). In this article, we present a literature review on post-valvular surgery CAS and report the clinical case of a 77 year-old man who experienced severe early post-aortic surgery chest pain and hemodynamic instability. Emergent coronary angiography revealed severe occlusion of multiple branches of both coronary arteries. The CAS was alleviated with intracoronary infusion of nitroglycerin.

A rare case of ALCAPA and rheumatic mitral valve regurgitation in an adult patient.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary artery defect leading to sudden cardiac death. Diagnosis is made after the onset of symptoms, mainly in the pediatric population. We describe an uncommon presentation of ALCAPA and rheumatic mitral valve regurgitation, diagnosed by a coronary 64-CT scan performed before a planned mitral valve repair operation.

Xenobiotic sensor- and metabolism-related gene variants in environmental sensitivity-related illnesses: a survey on the Italian population.

In the environmental sensitivity-related illnesses (SRIs), multiple chemical sensitivity (MCS), chronic fatigue syndrome (FCS), and fibromyalgia (FM), the search for genetic polymorphisms of phase I/II xenobiotic-metabolizing enzymes as suitable diagnostic biomarkers produced so far inconclusive results, due to patient heterogeneity, geographic/ethnic differences in genetic backgrounds, and different methodological approaches. Here, we compared the frequency of gene polymorphisms of selected cytochrome P450 (CYP) metabolizing enzymes and, for the first time, the frequency of the xenobiotic sensor Aryl hydrocarbon receptor (AHR) in the three cohorts of 156 diagnosed MCS, 94 suspected MCS, and 80 FM/FCS patients versus 113 healthy controls. We found significantly higher frequency of polymorphisms CYP2C9∗2, CYP2C9∗3, CYP2C19∗2, CYP2D6∗4 and CYP2D6∗41 in patients compared with controls. This confirms that these genetic variants represent a genetic risk factor for SRI. Moreover, the compound heterozygosity for CYP2C9∗2 and ∗3 variants was useful to discriminate between either MCS or FM/CFS versus SMCS, while the PM ∗41/∗41 genotype discriminated between MCS and either SMCS or FM/CFS. The compound heterozygosity for CYP2C9 ∗1/∗3 and CYP2D6 ∗1/∗4 differentiated MCS and SMCS cases from FM/CFS ones. Interestingly, despite the distribution of the AHR Arg554Lys variant did not result significantly different between SRI cases and controls, it resulted useful for the discrimination between MCS and SMCS cases when considered within haplotypes in combination with CYP2C19 ∗1/∗2 and CYP2D6 ∗1/∗4. Results allowed us to propose the genotyping for these specific CYP variants, together with the AHR Arg554Lys variant, as reliable, cost-effective genetic parameters to be included in the still undefined biomarkers' panel for laboratory diagnosis of the main types of environmental-borne SRI.

Glutathione peroxidase activity in the blood cells of psoriatic patients correlates with their responsiveness to Efalizumab.

Biological treatment of psoriasis, a chronic inflammatory immune-mediated pathology of huge social impact, has become a recent revolutionizing breakthrough in the management of the disease. Apart from anti-TNF-alpha biologics, recombinant proteins-inhibitors of the T lymphocytes-antigen presenting cells interaction, Efalizumab among them, have been successfully used in the therapy of psoriasis. Serious concern regarding safety and efficacy of biologics remains because they induce numerous adverse effects and a significant number of patients are non-responders. Up-to-now, there are no biochemical or/and immunological markers of the clinical efficacy of these drugs. This study searches for immunological and redox markers of the clinical response in the group of psoriatic patients treated with Efalizumab. Clinical response to Efalizumab was assessed by Psoriasis Area and Severity Index and correlated with suppression of T-cell functions, plasma cytokines, membrane-associated polyunsaturated fatty acids (PUFAs), antioxidant enzymes and markers of oxidative stress. A 12-week Efalizumab therapy did not affect abnormal plasma levels of pro-inflammatory cytokines and lower-than-normal content of PUFAs esterified in phospholipids of red cell membranes. It did, however, suppress T-cell-mediated functions and decrease nitrites/nitrates and malonyl dialdehyde levels independently on the clinical outcome. On contrast, activities of glutathione peroxidase (GPx) and glutathione S-transferase in granulocytes were remarkably increased and catalase decreased exclusively in non-responders vs complete or partial responders. High baseline GPx in erythrocytes decreased in responders. It is concluded that clinical response to Efalizumab correlates with GPx activity in the blood cells, suggesting that high hydroperoxide levels are involved in psoriasis persistence.

Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes.

BACKGROUND: Multiple chemical sensitivity (MCS) is a poorly clinically and biologically defined environment-associated syndrome. Although dysfunctions of phase I/phase II metabolizing enzymes and redox imbalance have been hypothesized, corresponding genetic and metabolic parameters in MCS have not been systematically examined. OBJECTIVES: We sought for genetic, immunological, and metabolic markers in MCS. METHODS: We genotyped patients with diagnosis of MCS, suspected MCS and Italian healthy controls for allelic variants of cytochrome P450 isoforms (CYP2C9, CYP2C19, CYP2D6, and CYP3A5), UDP-glucuronosyl transferase (UGT1A1), and glutathione S-transferases (GSTP1, GSTM1, and GSTT1). Erythrocyte membrane fatty acids, antioxidant (catalase, superoxide dismutase (SOD)) and glutathione metabolizing (GST, glutathione peroxidase (Gpx)) enzymes, whole blood chemiluminescence, total antioxidant capacity, levels of nitrites/nitrates, glutathione, HNE-protein adducts, and a wide spectrum of cytokines in the plasma were determined. RESULTS: Allele and genotype frequencies of CYPs, UGT, GSTM, GSTT, and GSTP were similar in the Italian MCS patients and in the control populations. The activities of erythrocyte catalase and GST were lower, whereas Gpx was higher than normal. Both reduced and oxidised glutathione were decreased, whereas nitrites/nitrates were increased in the MCS groups. The MCS fatty acid profile was shifted to saturated compartment and IFNgamma, IL-8, IL-10, MCP-1, PDGFbb, and VEGF were increased. CONCLUSIONS: Altered redox and cytokine patterns suggest inhibition of expression/activity of metabolizing and antioxidant enzymes in MCS. Metabolic parameters indicating accelerated lipid oxidation, increased nitric oxide production and glutathione depletion in combination with increased plasma inflammatory cytokines should be considered in biological definition and diagnosis of MCS.

Wide-spectrum profile of inflammatory mediators in the plasma and scales of patients with psoriatic disease.

Psoriasis is a chronic recurrent inflammatory disorder of the skin. Clinical subtypes include psoriasis vulgaris (PV), psoriatic arthropathy, and erythrodermic psoriasis. Aim of this study was to analyse relevant inflammatory mediators in the plasma of patients with distinct subtypes of active psoriasis, and in the scales of mild-to-moderate PV patients, and correlation to disease severity. Compared to healthy controls (n=10), patients affected by very severe forms of psoriasis (n=30) were characterized by increased plasma levels of IL-4, IL-6, MCP-1, VEGF and in particular PDGFbb. Each group with severe psoriasis had distinct characteristic features of plasma cytokine profile. Mild-to-moderate PV patients (n=35) showed higher levels of IL-4, IL-6, IL-10, and IL-13 when compared to healthy controls. No correlation was found between PV severity assessed by PASI (Psoriasis Area and Severity Index) and levels of these mediators. By contrast, disease severity correlated to scale levels of IP-10. For the first time, we found exaggerated circulating levels of the pro-angiogenic PDGFbb and VEGF in severe psoriasis. Evidence that the severity of skin symptoms correlated exclusively with scale levels of IP-10, but not with any up-regulated inflammatory mediator in plasma, suggests that distinct skin-independent processes contribute to the circulating cytokine profile in psoriasis.

How are 'Barack Obama' and 'President Elect' differentially stored in the brain? An ERP investigation on the processing of proper and common noun pairs.

BACKGROUND: One of the most debated issues in the cognitive neuroscience of language is whether distinct semantic domains are differentially represented in the brain. Clinical studies described several anomic dissociations with no clear neuroanatomical correlate. Neuroimaging studies have shown that memory retrieval is more demanding for proper than common nouns in that the former are purely arbitrary referential expressions. In this study a semantic relatedness paradigm was devised to investigate neural processing of proper and common nouns. METHODOLOGY/PRINCIPAL FINDINGS: 780 words (arranged in pairs of Italian nouns/adjectives and the first/last names of well known persons) were presented. Half pairs were semantically related ("Woody Allen" or "social security"), while the others were not ("Sigmund Parodi" or "judicial cream"). All items were balanced for length, frequency, familiarity and semantic relatedness. Participants were to decide about the semantic relatedness of the two items in a pair. RTs and N400 data suggest that the task was more demanding for common nouns. The LORETA neural generators for the related-unrelated contrast (for proper names) included the left fusiform gyrus, right medial temporal gyrus, limbic and parahippocampal regions, inferior parietal and inferior frontal areas, which are thought to be involved in the conjoined processing a familiar face with the relevant episodic information. Person name was more emotional and sensory vivid than common noun semantic access. CONCLUSIONS/SIGNIFICANCE: When memory retrieval is not required, proper name access (conspecifics knowledge) is not more demanding. The neural generators of N400 to unrelated items (unknown persons and things) did not differ as a function of lexical class, thus suggesting that proper and common nouns are not treated differently as belonging to different grammatical classes.

Acute effect of exercise-induced leg ischemia on cutaneous vasoreactivity in patients with stage II peripheral artery disease.

Conflicting data are available regarding the acute effect of exercise-provoked leg ischemia on the endothelial function in patients with stage II peripheral artery disease (PAD). In order to clarify this issue, cutaneous hyperemic responses to iontophoresis delivery of an endothelium-dependent (acetylcholine, ACh) and an endothelium-independent (sodium nitroprusside, SNP) vasodilator were evaluated under resting conditions, and before and after a treadmill test, using laser Doppler flowmetry, in 14 males (aged 68 +/- 4 years) affected by stage II PAD; 14 age-matched healthy males served as controls. At resting, a significantly reduced skin hyperemic response to ACh and to SNP was observed in PAD patients when compared to controls. Following treadmill, the leg skin hyperemic response to ACh delivery was significantly lower at peak of claudication than prior exercise (139 +/- 10 vs 213 +/- 25%, P = 0.01) in PAD patients, whereas no difference was observed in controls. The hyperemic response to SNP after exercise did not differ from baseline in either PAD patients or controls. The present data are in keeping with a reduced skin vasodilator capacity in stage II PAD patients at resting. In addition, the further impairment of skin endothelium-dependent vasodilation at the peak of claudication could indicate an acute endothelial dysfunction associated with exercise-induced leg muscle ischemia. These preliminary results also suggest that the threshold of claudication should not be exceeded during rehabilitation programs for PAD patients.

Endothelium-dependent and endothelium-independent skin vasoreactivity in the elderly.

BACKGROUND AND AIMS: It was demonstrated that endothelium-dependent vasoreactivity, an aspect of endothelial functioning, is impaired in coronary and brachial arteries, and in skeletal muscle resistance vessels of elderly people. However, little data is available about the influence of aging per se on the endothelial function of the skin microcirculation. The aim of the present study was to evaluate the endothelial function and intrinsic vasodilatory capacity of the skin microcirculation in elderly people with a low atherosclerosis risk profile. METHODS: Using laser Doppler flowmetry, we measured the cutaneous hyperemic responses following local iontophoresis delivery of an endothelium-dependent vasodilator, acetylcholine (ACh), and an endothelium-independent vasodilator, sodium nitroprusside (SNP), in 15 subjects older than 65 years and in 15 subjects younger than 50 years. Exclusion criteria were diabetes, hyperlipidemia, smoking, arterial hypertension and cardiovascular diseases. RESULTS: Skin maximal hyperemic responses induced both by ACh and by SNP delivery did not differ between the younger and the older groups. Cutaneous blood flow progressively increased in response to the 8 ACh delivery steps, both in the older and younger groups; however, the dose-response curve following ACh delivery was significantly lower in the former (p < 0.001). CONCLUSIONS: While these results should be viewed as preliminary due to the small sample size, they suggest that aging in itself is associated with a mild endothelium dysfunction in the skin microcirculation, whereas its overall vasodilatory capacity is preserved.