Total arterial off-pump surgery provides excellent outcomes and does not compromise complete revascularization†

OBJECTIVES The combination of aortic ‘no-touch' off-pump surgery (OPCAB) and total arterial revascularization (TAR) can reduce peri-procedural morbidity and yields excellent long-term outcomes albeit at a reported risk of incomplete revascularization. The feasibility of OPCAB-TAR with specific regards to the complete revascularization (CR) in patients with multi-vessel disease was evaluated. METHODS From 2003 to 2010, 712 patients underwent TAR including 526 patients who had OPCAB-TAR and 186 patients who received on-pump TAR [(ONCAB grafting (ONCABG)-TAR)]. Of these, 52% (n=272; OPCAB) vs. 83% (n=155; ONCABG) had triple-vessel disease (TVD). To balance patient characteristics, a non-parsimonious, propensity score (PS) model was applied. Endpoints evaluated were mortality, stroke, major adverse cardiac and cerebrovascular events (MACCE). To evaluate CR, an ‘Index of CR' (ICOR) was calculated, defined as the number of distal anastomoses divided by the number of the diseased coronary vessels. CR was assumed when the following requirements were fulfilled: the number of distal anastomoses was equal to or higher than that of diseased vessels (ICOR≥1), and all affected coronary territories (left anterior descending, circumflex artery and/or right coronary artery) were grafted. RESULTS Mortality was comparable between groups, whereas OPCAB patients suffered from significantly decreased rates of MACCE [3.0 vs. 7.0%; propensity-adjusted odd ratio (PAOR)=0.24; confidence interval (CI) 95% 0.08-0.66; P=0.006] including a clear trend towards reduced stroke and myocardial infarction. In the subgroup with TVD, OPCAB patients presented with significantly reduced rates for MACCE (1.8 vs. 5.8%; PAOR=0.07; CI 95% 0.01-0.65; P=0.02), including a significantly lower rate for stroke. For all-comers, the number of diseased vessels was lower after OPCAB (2.36±0.73 vs. 2.87±0.39; P<0.001) and consequently, these patients received an overall lower number of distal anastomoses (2.42±1.15 vs. 3.06±0.98; P<0.001). Although the ICOR was slightly lower (1.04±0.37 vs. 1.07±0.37; P=0.02), CR was achieved more frequently in OPCAB patients (82.1 vs. 73.1%; P=0.01). In the subgroup with TVD, the number of distal anastomoses (2.99±1.14 vs. 3.10±0.98; P=0.19) and the ICOR (1.00±0.38 vs. 1.03±0.33; P=0.19) was comparable between groups. The frequency of CR was slightly higher (75 vs. 67.7%; P=0.11), and the proportion of complete in situ grafting was significantly higher after OPCAB (37.1 vs. 23.9%; P=0.005). CONCLUSIONS Aortic ‘no-touch' OPCAB-TAR leads to a significant reduction of MACCE. It does not compromise CR in patients with TVD and thus can be safely applied to these patient

Total arterial off-pump surgery provides excellent outcomes and does not compromise complete revascularization†

OBJECTIVES The combination of aortic ‘no-touch' off-pump surgery (OPCAB) and total arterial revascularization (TAR) can reduce peri-procedural morbidity and yields excellent long-term outcomes albeit at a reported risk of incomplete revascularization. The feasibility of OPCAB-TAR with specific regards to the complete revascularization (CR) in patients with multi-vessel disease was evaluated. METHODS From 2003 to 2010, 712 patients underwent TAR including 526 patients who had OPCAB-TAR and 186 patients who received on-pump TAR [(ONCAB grafting (ONCABG)-TAR)]. Of these, 52% (n=272; OPCAB) vs. 83% (n=155; ONCABG) had triple-vessel disease (TVD). To balance patient characteristics, a non-parsimonious, propensity score (PS) model was applied. Endpoints evaluated were mortality, stroke, major adverse cardiac and cerebrovascular events (MACCE). To evaluate CR, an ‘Index of CR' (ICOR) was calculated, defined as the number of distal anastomoses divided by the number of the diseased coronary vessels. CR was assumed when the following requirements were fulfilled: the number of distal anastomoses was equal to or higher than that of diseased vessels (ICOR≥1), and all affected coronary territories (left anterior descending, circumflex artery and/or right coronary artery) were grafted. RESULTS Mortality was comparable between groups, whereas OPCAB patients suffered from significantly decreased rates of MACCE [3.0 vs. 7.0%; propensity-adjusted odd ratio (PAOR)=0.24; confidence interval (CI) 95% 0.08-0.66; P=0.006] including a clear trend towards reduced stroke and myocardial infarction. In the subgroup with TVD, OPCAB patients presented with significantly reduced rates for MACCE (1.8 vs. 5.8%; PAOR=0.07; CI 95% 0.01-0.65; P=0.02), including a significantly lower rate for stroke. For all-comers, the number of diseased vessels was lower after OPCAB (2.36±0.73 vs. 2.87±0.39; P<0.001) and consequently, these patients received an overall lower number of distal anastomoses (2.42±1.15 vs. 3.06±0.98; P<0.001). Although the ICOR was slightly lower (1.04±0.37 vs. 1.07±0.37; P=0.02), CR was achieved more frequently in OPCAB patients (82.1 vs. 73.1%; P=0.01). In the subgroup with TVD, the number of distal anastomoses (2.99±1.14 vs. 3.10±0.98; P=0.19) and the ICOR (1.00±0.38 vs. 1.03±0.33; P=0.19) was comparable between groups. The frequency of CR was slightly higher (75 vs. 67.7%; P=0.11), and the proportion of complete in situ grafting was significantly higher after OPCAB (37.1 vs. 23.9%; P=0.005). CONCLUSIONS Aortic ‘no-touch' OPCAB-TAR leads to a significant reduction of MACCE. It does not compromise CR in patients with TVD and thus can be safely applied to these patient

Negative microbiological results are not mandatory in deep sternal wound infections before wound closure†

OBJECTIVES To define the outcome of treatment for deep sternal wound infections (DSWIs) using direct wound closure (DC) or vacuum-assisted therapy (VAT) based on negative vs. positive microbiological results. METHODS Between 1999 and 2008, 7746 patients underwent median sternotomy for cardiac surgery at our institution. Patients were screened for DSWI and out of the cohort 159 were identified (2%). These patients were treated, either using DC or VAT with delayed wound closure. Outcomes were retrospectively analysed to determine the effect of negative cultures at the time of closure. RESULTS The indication for sternotomy was CABG 51%, isolated valve 18%, CABG/valve 18% and other related cardiovascular procedures 14%. Sixty-five percent of the wound infections was diagnosed during rehabilitation period. One hundred and five (66%) patients were treated with VAT vs. 54 (34%) patients with direct closure. Coagulase negative staphylococci were found in 48% of bacterial cultures. In 75% of the patients, the microbiological results were positive at time of wound closure (69.2% VAT vs. 87.0% direct closure, P=0.014). Out of 159 patients, 5.0% were with positive microbiological results at the time of closure readmitted vs. 5.1% with negative microbiological results (P=1.0). Patients with VAT stayed significantly longer in the hospital (mean 21±16 vs. 13±12, P=0.002). CONCLUSIONS Negative microbiological results are not mandatory before wound closure, as the rate of readmissions for recurrence of infection showed no difference between groups. Our results also suggest that shortening of VAT despite positive microbiological results may be feasibl

Corrigendum to: Management of Tricuspid Regurgitation: The Role of Transcatheter Therapies

Fabian Nietlispach, Michel Zuber and Francesco Maisano Heart Valve Clinic, University Hospital of Zurich, University of Zurich, Zurich, Switzerlan

Anisotropic topographies restore endothelial monolayer integrity and promote the proliferation of senescent endothelial cells

Thrombogenicity remains a major issue in cardiovascular implants (CVIs). Complete surficial coverage of CVIs by a monolayer of endothelial cells (ECs) prior to implantation represents a promising strategy but is hampered by the overall logistical complexity and the high number of cells required. Consequently, extensive cell expansion is necessary, which may eventually lead to replicative senescence. Considering that micro-structured surfaces with anisotropic topography may promote endothelialization, we investigated the impact of gratings on the biomechanical properties and the replicative capacity of senescent ECs. After cultivation on gridded surfaces, the cells showed significant improvements in terms of adherens junction integrity, cell elongation, and orientation of the actin filaments, as well as enhanced yes-associated protein nuclear translocation and cell proliferation. Our data therefore suggest that micro-structured surfaces with anisotropic topographies may improve long-term endothelialization of CVIs. Keywords: aging; anisotropy; endothelial cells; monolayer integrity; proliferation; senescence; telomere; topograph

NAD+ protects against EAE by regulating CD4+ T-cell differentiation

CD4+ T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD+) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing immune homeostasis through CD4+IFNγ+IL-10+ T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. We show that NAD+ regulates CD4+ T-cell differentiation through tryptophan hydroxylase-1 (Tph1), independently of well-established transcription factors. In the presence of NAD+, the frequency of T-bet−/− CD4+IFNγ+ T cells was twofold higher than wild-type CD4+ T cells cultured in conventional T helper 1 polarizing conditions. Our findings unravel a new pathway orchestrating CD4+ T-cell differentiation and demonstrate that NAD+ may serve as a powerful therapeutic agent for the treatment of autoimmune and other diseases

Mast cells regulate CD4+ T-cell differentiation in the absence of antigen presentation

Producción CientíficaBackground: Given their unique capacity for antigen uptake, processing, and presentation, antigen-presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. We have previously shown the role of nicotinamide adenine dinucleotide (NAD+) in T-cell differentiation independently of the cytokine milieu, whereas the precise mechanisms remained unknown. Objective: The objective of this study is to further dissect the mechanism of actions of NAD+ and determine the effect of APCs on NAD+-mediated T-cell activation. Methods: Isolated dendritic cells and bone marrow–derived mast cells (MCs) were used to characterize the mechanisms of action of NAD+ on CD4+ T-cell fate in vitro. Furthermore, NAD+-mediated CD4+ T-cell differentiation was investigated in vivo by using wild-type C57BL/6, MC−/−, MHC class II−/−, Wiskott-Aldrich syndrome protein (WASP)−/−, 5C.C7 recombination-activating gene 2 (Rag2)−/−, and CD11b-DTR transgenic mice. Finally, we tested the physiologic effect of NAD+ on the systemic immune response in the context of Listeria monocytogenes infection. Results: Our in vivo and in vitro findings indicate that after NAD+ administration, MCs exclusively promote CD4+ T-cell differentiation, both in the absence of antigen and independently of major APCs. Moreover, we found that MCs mediated CD4+ T-cell differentiation independently of MHC II and T-cell receptor signaling machinery. More importantly, although treatment with NAD+ resulted in decreased MHC II expression on CD11c+ cells, MC-mediated CD4+ T-cell differentiation rendered mice resistant to administration of lethal doses of L monocytogenes. Conclusions: Collectively, our study unravels a novel cellular and molecular pathway that regulates innate and adaptive immunity through MCs exclusively and underscores the therapeutic potential of NAD+ in the context of primary immunodeficiencies and antimicrobial resistance.National Institutes of Health (grants R01NS073635 , R01MH110438 , R01HL096795 , U01HL126497 and R01AG039449)Instituto de Salud Carlos III (grant PI10/02 511)Fundación Ramón Areces (grant CIVP16A1843

Aspects of Tryptophan and Nicotinamide Adenine Dinucleotide in Immunity: A New Twist in an Old Tale

Increasing evidence underscores the interesting ability of tryptophan to regulate immune responses. However, the exact mechanisms of tryptophan’s immune regulation remain to be determined. Tryptophan catabolism via the kynurenine pathway is known to play an important role in tryptophan’s involvement in immune responses. Interestingly, quinolinic acid, which is a neurotoxic catabolite of the kynurenine pathway, is the major pathway for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that NAD+, a natural coenzyme found in all living cells, regulates immune responses and creates homeostasis via a novel signaling pathway. More importantly, the immunoregulatory properties of NAD+ are strongly related to the overexpression of tryptophan hydroxylase 1 (Tph1). This review provides recent knowledge of tryptophan and NAD+ and their specific and intriguing roles in the immune system. Furthermore, it focuses on the mechanisms by which tryptophan regulates NAD+ synthesis as well as innate and adaptive immune responses