SYNTAX II and SYNTAX III trials: What is the take home message for surgeons?

Percutaneous coronary intervention (PCI) has evolved greatly in the last 40 years since its introduction by Andreas Grüntzig in 1977. Since then, we've observed an evolution in balloons, the development of stents, changes in stent structure, development of drug eluting stents, improvements in strut design, thickness and even their polymeric coating. Most recently we saw the rise and "fall" of bioabsorbable scaffolds for PCI. Trials with the most diverse devices for PCI and diagnostic techniques have been conducted. Two of the most recent trials were reported in the last year and deserve special attention-SYNTAX II and SYNTAX III. These trials are completely different in design but present valuable information for doctors managing coronary artery disease (CAD). Both trials take into account contemporary technology for assessing and treating CAD. The first uses so-called "state-of-the-art" PCI and compares the outcomes of that approach with the outcomes of the PCI arm of the pivotal SYNTAX trial. SYNTAX III Revolution on the other hand does not focus on clinical endpoints: it is a blinded trial that does not randomize patients but randomizes doctors ("the heart team") to make a decision on the best treatment for complex CAD. This decision was based either on multi-slice CT with physiological assessment using FFRCT or on conventional angiography. In this review we bring the most important aspects of those trials and the key messages for surgeons together; also, what the surgeon may expect in the future after the publication of these interesting concepts

Estudo comparativo entre as manifestações oftalmológicas, sorológicas e resposta terapêutica de pacientes com esclerite isolada e esclerite associada a doenças sistêmicas

INTRODUCTION: Scleritis is a rare, progressive and serious disease, the signs of which are inflammation and edema of episcleral and scleral tissues and is greatly associated with systemic rheumatoid diseases. PURPOSE: To perform a prospective and comparative study between ophthalmologic manifestations, serologic findings and therapeutic response of patients with isolated scleritis and scleritis associated with systemic rheumatoid disease. METHODS: Thirty-two outpatients with non-infectious scleritis were studied, from March 2006 to March 2008. The treatment was corticoid eye drops associated with anti-inflammatory agents, followed by systemic corticoids and immunosuppressive drugs if necessary, was considered successful after six months without scleritis recurrence. RESULTS: Fourteen of 32 patients had scleritis associated with systemic rheumatoid disease, of which nine had rheumatoid arthritis, two systemic lupus erythematosus, one Crohn's disease, one Behçet's disease and one gout. There were no difference in relation to involvement and ocular complications, there was predominance of nodular anterior scleritis and scleral thinning was the most frequent complication. The scleritis associated with systemic rheumatoid disease group had 64.3% of autoantibodies, versus 27.8% among those with isolated scleritis and this difference was statistically significant. In the isolated scleritis group 16.7% used anti-inflammatory, 33.3% corticosteroids, 27.8% corticosteroids with one immunosuppressive drug, 5.5% two immunosuppressive drugs, 16.7% corticosteroids with two immunosuppressive drugs and 33.3% pulse of immunosuppressive drugs, there was remission in 88.9%. In the scleritis associated with systemic rheumatoid disease group 7.1% used anti-inflammatory, 7.1% corticosteroids, 50% corticosteroids with one immunosuppressive drug, 7.1% two immunosuppressive drugs and 22.2% pulse of immunosuppressive drugs, 100% had treatment success. CONCLUSION: Prevalence of unilateral nodular scleritis was noted in both groups and higher rates of all the parameters tested were noted in the scleritis associated with systemic rheumatoid disease group. There were no differences between the groups with respect to the use of immunosuppressive drugs and therapeutic response, which was fully satisfactory in the scleritis associated with systemic rheumatoid disease group and satisfactory in the isolated scleritis group.INTRODUÇÃO: Esclerite é uma doença grave, rara e progressiva, que envolve inflamação e edema dos tecidos episcleral superficial, profundo e escleral e está associada com doenças sistêmicas reumatológicas em muitos casos. OBJETIVOS: Realizar um estudo prospectivo comparativo entre as manifestações oftalmológicas, achados sorológicos e resposta terapêutica de pacientes com esclerite isolada e com esclerite associada a doenças sistêmicas reumatológicas. MÉTODOS: Trinta e dois pacientes com esclerite não infecciosa participaram do estudo, de março de 2006 a março de 2008. O tratamento realizado baseou-se no uso de colírios de corticoides associados aos anti-inflamatórios não-hormonais, seguidos de corticoides sistêmicos e imunossupressores, se necessário. O sucesso do tratamento foi considerado como seis meses sem crises de esclerite. RESULTADOS: Quatorze dos 32 pacientes apresentaram esclerite associada à doença sistêmica, dos quais nove com artrite reumatóide, dois com lúpus eritematoso sistêmico, um com doença de Crohn, um com doença de Behçet e um com gota. Não houve diferenças em relação ao envolvimento ocular e suas complicações, predominando a esclerite anterior nodular e o afinamento escleral, respectivamente. O grupo com esclerite associada a doenças sistêmicas apresentou 64,3% de positividade de autoanticorpos contra 27,8% no grupo com esclerite isolada, sendo tal diferença estatisticamente significante. No grupo com esclerite isolada, 16,7% fez uso de apenas anti-inflamatórios, 33,3% de corticoide sistêmico, 27,8% de corticoide com um imunossupressor, 5,5% dois imunossupressores, 16,7% corticoide com dois imunossupressores e 33,3% pulsoterapia com imunossupressor; sendo que houve sucesso do tratamento em 88,9%. No grupo com esclerite associada à doença sistêmica, 7,1% fez uso de anti-inflamatórios, 7,1% corticoide sistêmico, 50% corticoide com um imunossupressor, 7,1% dois imunossupressores e 22,2% pulsoterapia com imunossupressor; com 100% de sucesso no tratamento nesse grupo. CONCLUSÃO: Em ambos os grupos houve predomínio da esclerite nodular unilateral e o grupo com esclerite associada a doença sistêmica apresentou taxas maiores de todos os autoanticorpos testados. Não houve diferença entre os grupos em relação ao uso de imunossupressores e à resposta terapêutica, a qual foi totalmente satisfatória no grupo com esclerite associada à doença sistêmica e satisfatória no grupo com esclerite isolada.Universidade Federal de São Paulo (UNIFESP)Universidade de Santo AmaroUniversidade Federal de São Paulo (UNIFESP) Departamento de Oftalmologia Setor de Doenças Externas Oculares e CórneaUNIFESP, Depto. de Oftalmologia Setor de Doenças Externas Oculares e CórneaSciEL

Delineation of management zones using mobile measurements of soil apparent electrical conductivity and multivariate geostatistical techniques

Site-specific management promotes the identification and management of areas within the field, which represent subfield regions with homogeneous characteristics (management zones). However, determination of subfield areas is difficult because of the complex combination of factors which could affect crop yield. One possibility to capture yield variability is the use of soil physical properties to define the management zones as they are related to plant available water. With the aim of characterizing the spatial variability of the main soil physical variables and using this information to determine potential management zones, soil samples were taken from 70 locations in a 33-ha field in Badajoz, southwestern Spain. Firstly, accurate spatial distribution maps of the soil attributes were generated by using regression kriging as the most suitable algorithm in which exhaustive secondary information on soil apparent electrical conductivity (ECa) was incorporated. ECa measurements were carried out with a Veris 3100 operating in both shallow (0–30 cm), ECs, and deep (0–90 cm), ECd,mode. Clay, coarse sand and fine sand were the soil physical properties which exhibited higher correlation with ECa (positively correlated with the finer texture component, clay, and negatively correlated with the coarser ones, coarse and fine sands), particularly with ECs. Thus, this was the secondary variable used to obtain the kriged maps. Later, principal component analysis and fuzzy cluster classification were performed to delineate management zones, resulting in two subfields to be managed separately. This number of subfields was determined using the fuzzy performance index and normalized classification entropy as the way to optimize the classification algorithm

Anomalous septal perforator artery arising from the proximal right coronary artery

The interventricular septum is the most densely vascularized portion of the heart, containing important elements of the cardiac conduction system and providing mechanical support for both right and left ventricular function. The diagnosis and understanding of anomalies in coronary circulation are important when surgical or percutaneous myocardial revascularization is required. We report the case of a patient with an anomalous septal perforator artery arising from the proximal portion of the right coronary artery.O septo interventricular é uma das regiões mais vascularizadas do coração, contendo elementos importantes do sistema de condução cardíaco e fornecendo suporte mecânico para as funções ventriculares esquerda e direita. O diagnóstico e a compreensão das anomalias na circulação coronária são importantes quando a revascularização miocárdica, cirúrgica ou percutânea, é necessária. Descrevemos a seguir o caso de um paciente com artéria septal perfurante anômala originando-se da porção proximal da artéria coronária direita.939

Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus

BACKGROUND: The molecular mechanisms involved in the genesis of the adrenocortical lesions seen in MEN1 syndrome (ACL-MEN1) remain poorly understood; loss of heterozygosity at 11q13 and somatic mutations of MEN1 are not usually found in these lesions. Thus, additional genes must be involved in MEN1 adrenocortical disorders. Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. However, to our knowledge, the status of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions in MEN1 has not been previously investigated. OBJECTIVE: To evaluate glucose-dependent insulinotropic peptide receptor expression in adrenocortical hyperplasia associated with MEN1 syndrome. MATERIALS/METHODS: Three adrenocortical tissue samples were obtained from patients with previously known MEN1 germline mutations and in whom the presence of a second molecular event (a new MEN1 somatic mutation or an 11q13 loss of heterozygosity) had been excluded. The expression of the glucose-dependent insulinotropic peptide receptor was quantified by qPCR using the DDCT method, and b-actin was used as an endogenous control. RESULTS: The median of glucose-dependent insulinotropic peptide receptor expression in the adrenocortical lesions associated with MEN1 syndrome was 2.6-fold (range 1.2 to 4.8) higher than the normal adrenal controls (p = 0.02). CONCLUSION: The current study represents the first investigation of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions without 11q13 loss of heterozygosity in MEN1 syndrome patients. Although we studied a limited number of cases of MEN1 adrenocortical lesions retrospectively, our preliminary data suggest an involvement of glucose-dependent insulinotropic peptide receptor overexpression in the etiology of adrenocortical hyperplasia. New prospective studies will be able to clarify the exact role of the glucose-dependent insulinotropic peptide receptor in the molecular pathogenesis of MEN1 adrenocortical lesions

Impact of non-respect of SYNTAX score II recommendation for surgery in patients with left main coronary artery disease treated by percutaneous coronary intervention: an EXCEL substudy

OBJECTIVES: The SYNTAX score II (SSII) was developed from the SYNTAX trial to predict the 4-year all-cause mortality after left main or multivessel disease revascularization and to facilitate the decision-making process. The SSII provides the following treatment recommendations: (i) coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (equipoise risk), (ii) CABG preferred (excessive risk for PCI) or (iii) PCI preferred (excessive risk for CABG). We sought to externally validate SSII and to investigate the impact of not abiding by the SSII recommendations in the randomized EXCEL trial of PCI versus CABG for left main disease. METHODS: The calibration plot of predicted versus observed 4-year mortality was constructed from individual values of SSII in EXCEL. To assess overestimation versus underestimation of predicted mortality risk, an optimal fit regression line with slope and intercept was determined. Prospective treatment recommendations based on SSII were compared with actual treatments and all-cause mortality at 4 years. RESULTS: SSII variables were available from EXCEL trial in 1807/1905 (95%) patients. For the entire cohort, discrimination was possibly helpful (C statistic = 0.670). SSII-predicted all-cause mortality at 4 years overestimated the observed mortality, particularly in the highest-risk percentiles, as confirmed by the fit regression line [intercept 2.37 (1.51-3.24), P = 0.003; slope 0.67 (0.61-0.74), P < 0.001]. When the SSII-recommended treatment was CABG, randomized EXCEL patients treated with PCI had a trend towards higher mortality compared with those treated with CABG (14.1% vs 5.3%, P = 0.07) in the as-treat population. In the intention-to-treat population, patients randomized to PCI had higher mortality compared with those randomized to CABG (15.1% vs 4.1%, P = 0.02), when SSII recommended CABG. CONCLUSIONS: In the EXCEL trial of patients with left main disease, the SSII-predicted 4-year mortality overestimated the 4-year observed mortality with a possibly helpful discrimination. Non-compliance with SSII CABG treatment recommendations (i.e. randomized to PCI) was associated with higher 4-year all-cause mortality

Mutagenic Potential of Bos taurus

Bovine papillomavirus (BPV) is considered a useful model to study HPV oncogenic process. BPV interacts with the host chromatin, resulting in DNA damage, which is attributed to E5, E6, and E7 viral oncoproteins activity. However, the oncogenic mechanisms of BPV E6 oncoprotein per se remain unknown. This study aimed to evaluate the mutagenic potential of Bos taurus papillomavirus type 1 (BPV-1) E6 recombinant oncoprotein by the cytokinesis-block micronucleus assay (CBMNA) and comet assay (CA). Peripheral blood samples of five calves were collected. Samples were subjected to molecular diagnosis, which did not reveal presence of BPV sequences. Samples were treated with 1 μg/mL of BPV-1 E6 oncoprotein and 50 μg/mL of cyclophosphamide (positive control). Negative controls were not submitted to any treatment. The samples were submitted to the CBMNA and CA. The results showed that BPV E6 oncoprotein induces clastogenesis per se, which is indicative of genomic instability. These results allowed better understanding the mechanism of cancer promotion associated with the BPV E6 oncoprotein and revealed that this oncoprotein can induce carcinogenesis per se. E6 recombinant oncoprotein has been suggested as a possible vaccine candidate. Results pointed out that BPV E6 recombinant oncoprotein modifications are required to use it as vaccine

Impact of coronary calcification assessed by coronary CT angiography on treatment decision in patients with three-vessel CAD:insights from SYNTAX III trial

 : OBJECTIVES: The aim of this study was to determine Syntax scores based on coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) and to assess whether heavy coronary calcification significantly limits the CCTA evaluation and the impact of severe calcification on heart team’s treatment decision and procedural planning in patients with three-vessel coronary artery disease (CAD) with or without left main disease. METHODS: SYNTAX III was a multicentre, international study that included patients with three-vessel CAD with or without left main disease. The heart teams were randomized to either assess coronary arteries with coronary CCTA or ICA. We stratified the patients based on the presence of at least 1 lesion with heavy calcification defined as arc of calcium >180° within the lesion using CCTA. Agreement on the anatomical SYNTAX score and treatment decision was compared between patients with and without heavy calcifications. RESULTS: Overall, 222 patients with available CCTA and ICA were included in this trial subanalysis (104 with heavy calcification, 118 without heavy calcification). The mean difference in the anatomical SYNTAX score (CCTA derived—ICA derived) was lower in patients without heavy calcifications [mean (−1.96 SD; +1.96 SD) = 1.5 (−19.3; 22.4) vs 5.9 (−17.5; +29.3), P = 0.004]. The agreement on treatment decision did not differ between patients with (Cohen’s kappa 0.79) or without coronary calcifications (Cohen’s kappa 0.84). The agreement on the treatment planning did not differ between patients with (concordance 80.3%) or without coronary calcifications (concordance 82.8%). CONCLUSIONS: An overall good correlation between CCTA- and ICA-derived Syntax score was found. The presence of heavy coronary calcification moderately influenced the agreement between CCTA and ICA on the anatomical SYNTAX score. However, agreement on the treatment decision and planning was high and irrespective of the presence of calcified lesions

The impact of plaque type on strut embedment/protrusion and shear stress distribution in bioresorbable scaffold

AIMS: Scaffold design and plaque characteristics influence implantation outcomes and local flow dynamics in treated coronary segments. Our aim is to assess the impact of strut embedment/protrusion of bioresorbable scaffold on local shear stress distribution in different atherosclerotic plaque types. METHODS AND RESULTS: Fifteen Absorb everolimus-eluting Bioresorbable Vascular Scaffolds were implanted in human epicardial coronary arteries. Optical coherence tomography (OCT) was performed post-scaffold implantation and strut embedment/protrusion were analysed using a dedicated software. OCT data were fused with angiography to reconstruct 3D coronary anatomy. Blood flow simulation was performed and wall shear stress (WSS) was estimated in each scaffolded surface and the relationship between strut embedment/protrusion and WSS was evaluated. There were 9083 struts analysed. Ninety-seven percent of the struts (n = 8840) were well-apposed and 243 (3%) were malapposed. At cross-section level (n = 1289), strut embedment was significantly increased in fibroatheromatous plaques (76 ± 48 µm) and decreased in fibrocalcific plaques (35 ± 52 µm). Compatible with strut embedment, WSS was significantly higher in lipid-rich fibroatheromatous plaques (1.50 ± 0.81 Pa), whereas significantly decreased in fibrocalcified plaques (1.05 ± 0.91 Pa). After categorization of WSS as low (<1.0 Pa) and normal/high WSS (≥1.0 Pa), the percent of low WSS in the plaque subgroups were 30.1%, 31.1%, 25.4%, and 36.2% for non-diseased vessel wall, fibrous plaque, fibroatheromatous plaque, and fibrocalcific plaque, respectively (P-overall < 0.001). CONCLUSION: The composition of the underlying plaque influences strut embedment which seems to have effect on WSS. The struts deeply embedded in lipid-rich fibroatheromas plaques resulted in higher WSS compared with the other plaque types