Use of paclitaxel carried in lipid nanoparticles to treat aortic allograft transplantation in rats.

OBJECTIVES: The aim of this study was to test whether lipid core nanoparticles loaded with paclitaxel (LDE-PTX) protect rat aortic allograft from immunological damage. METHODS: Fisher and Lewis rats were used differing in minor histocompatibility loci. Sixteen Lewis rats were allocated to four-animal groups: SYNG (syngeneic), Lewis rats receiving aorta grafts from Lewis rats; ALLO (allogeneic), Lewis rats receiving aortas from Fisher rats; ALLO+LDE (allogeneic transplant treated with LDE), Lewis rats receiving aortas from Fisher rats, treated with LDE (weekly injection for 3 weeks); ALLO+LDE-PTX (allogeneic transplant treated with LDE-PTX), Lewis rats receiving aortas from Fisher rats treated with LDE-PTX (4 mg/kg weekly for 3 weeks). Treatments began on transplantation day. RESULTS: Thirty days post-transplantation, SYNG showed intact aortas. ALLO and ALLO+LDE presented intense neointimal formation. In ALLO+LDE-PTX, treatment inhibited neointimal formation; narrowing of aortic lumen was prevented in ALLO and ALLO+LDE. LDE-PTX strongly inhibited proliferation and intimal invasion by smooth muscle cells, diminished 4-fold presence of apoptotic/dead cells in the intima, reduced the invasion of aorta by macrophages and T-cells and gene expression of pro-inflammatory tumour necrosis factor-alpha (TNFα), interferon gamma (IFNγ) and interleukin-1 beta (IL-1ß). CONCLUSIONS: LDE-PTX was effective in preventing the vasculopathy associated with rejection and may offer a potent therapeutic tool for post-transplantation.

Does Prior Percutaneous Coronary Intervention Influence the Outcomes of Coronary Artery Bypass Surgery?

INTRODUCTION: Percutaneous coronary intervention (PCI) has been increasingly performed to treat coronary artery disease. The performance of multiple PCI has also been increasing. Consequently, the percentage of patients presenting for coronary artery bypass graft (CABG) surgery is reported to vary from 13 to 40%. The influence of previous PCI on CABG outcomes has been studied in single center, regional studies, registries and meta-analyses. Some reports showed a negative effect on mortality and morbidity in early or long-term follow-up, but others did not find this influence. METHODS AND RESULTS: A cohort of 3007 patients consecutively operated for CABG, 261 of them with previous PCI, were included in this analysis. Comparison of the groups "previous PCI" and "primary CABG" was made in the original cohort and in a propensity score matched cohort of 261 patients. There were some differences in preoperative clinical characteristics in both types of cohort, even in the matched one. Outcomes were compared at 30 days, 1 year and 5 years of follow-up. There were no statistically significant differences in mortality in any period or cohort. There were some differences in other outcomes as readmission and composite events, including cardiovascular death at 1 and 5 years of follow-up. These differences, neverthless, were not confirmed in comparison with the matched cohort. CONCLUSION: Although there are some limitations in this study, it was not found consistent negative influence of previous PCI on CABG.

Does prior percutaneous coronary intervention influence the outcomes of coronary artery bypass surgery?

Abstract Introduction: Percutaneous coronary intervention (PCI) has been increasingly performed to treat coronary artery disease. The performance of multiple PCI has also been increasing. Consequently, the percentage of patients presenting for coronary artery bypass graft (CABG) surgery is reported to vary from 13 to 40%. The influence of previous PCI on CABG outcomes has been studied in single center, regional studies, registries and meta-analyses. Some reports showed a negative effect on mortality and morbidity in early or long-term follow-up, but others did not find this influence. Methods and Results: A cohort of 3007 patients consecutively operated for CABG, 261 of them with previous PCI, were included in this analysis. Comparison of the groups "previous PCI" and "primary CABG" was made in the original cohort and in a propensity score matched cohort of 261 patients. There were some differences in preoperative clinical characteristics in both types of cohort, even in the matched one. Outcomes were compared at 30 days, 1 year and 5 years of follow-up. There were no statistically significant differences in mortality in any period or cohort. There were some differences in other outcomes as readmission and composite events, including cardiovascular death at 1 and 5 years of follow-up. These differences, neverthless, were not confirmed in comparison with the matched cohort. Conclusion: Although there are some limitations in this study, it was not found consistent negative influence of previous PCI on CABG.

Desenvolvimento de modelo clínico para predição da possibilidade de identificação da artéria de Adamkiewicz por angiotomografia / Development of a clinical model to predict the likelihood of identification of the Adamkiewicz artery by angiotomography

Contexto: Diferenças morfológicas da artéria de Adamkiewicz (AKA) entre a população portadora e não portadora de doença aórtica têm importância clínica, influenciando as complicações neuroisquêmicas da medula espinhal em procedimentos operatórios. Ainda não é conhecida a correlação entre parâmetros clínicos e a previsibilidade da identificação dessa artéria pela angiotomografia. Objetivo: Desenvolver um modelo matemático que, através de parâmetros clínicos correlacionados com aterosclerose, possa prever a probabilidade de identificação da AKA em pacientes submetidos a angiotomografias. Método: Estudo observacional transversal utilizando banco de imagens e dados de pacientes. Foi feita análise estatística multivariada e criado modelo matemático logit de predição para identificação da AKA. Variáveis significativas foram utilizadas na montagem da fórmula para cálculo da probabilidade de identificação. O modelo foi calibrado, e a discriminação foi avaliada pela curva receiver operating characteristic (ROC). A seleção das variáveis explanatórias foi guiada pela maior área na curva ROC (p = 0,041) e pela significância combinada das variáveis. Resultados: Foram avaliados 110 casos (54,5% do sexo masculino, com idade média de 60,97 anos e etnia com coeficiente B -2,471, M -1,297, N -0,971), com AKA identificada em 60,9%. Índice de massa corporal: 27,06 ± 0,98 (coef. -0,101); fumantes: 55,5% (coef. -1,614/-1,439); diabéticos: 13,6%; hipertensos: 65,5% (coef. -1,469); dislipidêmicos: 58,2%; aneurisma aórtico: 38,2%; dissecção aórtica: 12,7%; e trombo mural: 24,5%. Constante de 6,262. Fórmula para cálculo da probabilidade de detecção: ( ) ( ) . . . . . tan 1 ( 1) Coef Etnia Coef IMC IMC Coef fumante Coef HAS Coe f dislip Cons te e − + ×+ + + + − + . O modelo de predição foi criado e disponibilizado no link https://vascular.pro/aka-model. Conclusão: Com as covariáveis etnia, índice de massa corporal, tabagismo, hipertensão arterial e dislipidemia, foi possível criar um modelo matemático de predição de identificação da AKA com significância combinada de nove coeficientes (p = 0,042)

Background: There are clinically important morphological differences in the Adamkiewicz artery (AKA) between populations that do and do not have aortic disease and they have an influence on the neuroischemic complications involving the spinal cord during surgical operations. It is not yet known whether clinical parameters correlate with the predictability of identification of the artery using angiotomography. Objective: To develop a mathematical model that by correlating clinical parameters with atherosclerosis enables prediction of the probability of identification of the AKA in patients examined with angiotomography. Method: This is a cross-sectional, observational study using a patient database and image bank. A multivariate statistical analysis was conducted and a logit mathematical model was constructed to predict AKA identification. Significant variables were used to build a formula for calculation of the probability of identification. This model was calibrated and its power of discrimination was assessed using receiver operating characteristic (ROC) curves. Selection of explanatory variables was based on largest area under the ROC curve (p = 0.041) and combined significance of variables. Results: A total of 110 cases were analyzed (54.5% were male, mean age was 60.97 years, and ethnicity coefficients were white -2.471, brown -1.297, and black -0.971) and the AKA was identified in 60.9%. Body mass index: 27.06 ± 0.98 (coef. -0.101); smokers: 55.5% (coef. -1.614/-1.439); diabetes: 13.6%; hypertension: 65.5% (coef. -1.469); dyslipidemia: 58.2%; aortic aneurysm: 38.2%; aortic dissection: 12.7%; and mural thrombus: 24.5%. The constant was 6.262. The formula for calculating the probability of detection is as follows: ( ) ( ) . . . ker . . tan 1 ( 1) Coef Etnicity Coef BMI BMI Coef smo Coef SAH Coef dyslip Cons t e − + ×+ + + + − + . The prediction model was constructed and made available at: https://vascular.pro/aka-model. Conclusions: Using the covariates ethnicity, body mass index, smoking, arterial hypertension, and dyslipidemia, it proved possible to create a mathematical model for predicting identification of the AKA with a combined significance of nine coefficients (p = 0.042)

Predictors of Adamkiewicz artery and anterior spinal artery detection through computerized tomographic angiography.

BACKGROUND: The detection of the Adamkiewicz artery and the anterior spinal artery has been associated with the ability to prevent adverse spinal cord outcomes after aortic surgical procedures. Yet, to our knowledge, no previous studies have attempted to use modern predictive models to identify the most important variables in determining artery detectability. AIMS: To develop a model to predict the odds of visualizing the Adamkiewicz artery or anterior spinal artery in patients undergoing computerized tomographic angiography. METHODS: We conducted a prospective, cross-sectional study. Outcomes of interest were the non-detection of the Adamkiewicz artery and anterior spinal artery, and their corresponding level of origin. Axial images were inspected in high definition in search of two dense spots characterizing the Adamkiewicz artery and anterior spinal artery. A multiplanar three-dimensional reconstruction was then performed using the OsiriX® software. RESULTS: A total of 110 participants were part of this analysis. When evaluating risks for the Adamkiewicz artery being undetectable, significant factors could be classified into three broad categories: risk factors for arterial disease, established arterial disease, and obesity. Factors in the former category included metabolic syndrome, hypertension, and smoking status, while factors in the arterial disease included descending aortic aneurysm, mural thrombi, aortic aneurysm without a dissection, and aortic disease in general. In relation to anterior spinal artery not being detectable, significant risk factors included hypertension, smoking status, and metabolic syndrome, while those associated with arterial disease involved aortic disease and arterial thrombi. When evaluating the importance of individual clinical factors, the presence of higher body mass index was the single most important risk factor. CONCLUSION: Arterial disease, established arterial disease, and increased body mass index are risk factors in the detection of Adamkiewicz artery and anterior spinal artery. Specific diagnostic protocols should be in place for patients with these underlying conditions, thus enhancing the likelihood of detection when the Adamkiewicz artery is indeed present.

Influential Factors on the Evaluation of Adamkiewicz Artery Using a 320-Detector Row Computed Tomography Device.

BACKGROUND: Understanding the difference of Adamkiewicz artery (AKA) presentation in healthy and diseased subjects, and the influence of atherosclerotic factors prevalent in aortic disease patients, are important for aortic disease therapeutic planning. This study used a 320-detector row computed tomography (CT) device to examine the impact of clinical aspects of AKA identification in individuals with and without aortic disease. METHODS: Angio-CTs obtained from 115 patients were assessed and the individuals grouped according to the presence or absence of aortic disease. Datasets were analyzed using OsiriX software, and AKA was identified by three-dimensional multiplanar reconstruction. RESULTS: The group without aortic disease (Group A) comprised 32 (52.5%) men and 29 women, with a mean age of 53.7 ± 16.8 years. The group with aortic disease (Group B) comprised 31 (57.4%) men and 23 women, with a mean age of 64.8 ± 11.6 years. AKA was identified in 49 (80.3%) participants of Group A and 23 (42.6%) individuals of Group B (P ≤ 0.0001). In 53 cases (73.6%), AKA originated on the left side. AKA was mainly detected on the left side (73.6%), at the level of T10 to T12 (70%). Tobacco smokers, former smokers, and hypertensive patients had increased odds of having undetected AKA. CONCLUSIONS: Using the method described and a state of the art 320-detector row CT device, AKA was detected more frequently among individuals without aortic disease. Thus, aortic disease and atherosclerotic risk factors hindered AKA detection.

Influence of Drugs Carried in Lipid Nanoparticles in Coronary Disease of Rabbit Transplanted Heart.

BACKGROUND: Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and currently has no effective prevention and treatment. Lipid nanoparticles, termed LDE can carry chemotherapeutic agents in the circulation and concentrates them in the heart. METHODS: Twenty-eight rabbits fed a cholesterol-rich diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg/kg daily) and allocated to four groups of 7 animals treated with intravenous LDE-methotrexate (MTX; 4 mg/kg weekly), with LDE-paclitaxel (PACLI; 4 mg/kg weekly), or with LDE-PACLI (4 mg/kg weekly) and LDE-MTX (4 mg/kg weekly). A control group was treated with only weekly intravenous saline solution. Animals were euthanized 6 weeks later for morphometric, histologic, immunohistochemical, and gene expression analysis of the graft and native hearts. RESULTS: Compared with controls, grafts of rabbits treated with LDE-PACLI showed 50% reduction of coronary stenosis, and in the LDE-MTX and LDE-MTX/PACLI stenosis was approximately 18% less than in control, but this difference was not statistically significant. In the three treatment groups, macrophage infiltration was decreased. In the LDE-MTX group, gene expression of proinflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein 1, interleukin 18, vascular cellular adhesion molecule 1, and matrix metalloproteinase 12 was strongly diminished, whereas expression of antiinflammatory interleukin 10 increased. In the LDE-PACLI and LDE-PACLI/MTX groups, proinflammatory and antiinflammatory gene expressions were not consistently changed by the treatments. CONCLUSIONS: LDE-PACLI promoted strong improvement of cardiac allograft vasculopathy, but the decrease in coronary stenosis by LDE-MTX and LDE-MTX/PACLI was not significant. All three treatments decreased macrophage infiltration in the graft. These results may encourage future clinical trials to test this new therapeutic approach to coronary allograft vasculopathy.

Anatomia da circulação medular / Anatomy of spinal blood supply

A intrincada anatomia tridimensional da irrigação medular é frequentemente explanada na literatura com diferentes nomenclaturas e devido a sua alta relevância no estudo da isquemia medular, o estudo da terminologia se faz necessário para melhor compreensão do tema. A artéria de Adamkiewicz, também chamada de artéria radicular magna, é a via principal. Foi realizada a revisão da literatura com equiparação das nomenclaturas utilizadas e elaboração de descrição acurada e sumarizada do conhecimento atual sobre a vascularização medular.

The intricate three-dimensional vascular anatomy of the spinal cord is still not completely understood, and its terminology varies between studies. In view of its importance in spinal ischemia, an analysis is needed of the anatomic vocabulary used to describe the spinal cord blood supply to improve understanding of the subject. The main supply is the Adamkiewicz artery, also known as great anterior radicular artery. The literature was reviewed to equate the different nomenclatures employed and an accurate description of current knowledge on spinal cord vascularization was prepared.

Long-Term and Sustained Therapeutic Results of a Specific Promonocyte Cell Formulation in Refractory Angina: ReACT(®) (Refractory Angina Cell Therapy) Clinical Update and Cost-Effective Analysis.

Mononuclear stem cells have been studied for their potential in myocardial ischemia. In our previous published article, ReACT(®) phase I/II clinical trial, our results suggest that a certain cell population, promonocytes, directly correlated with the perceived angiogenesis in refractory angina patients. This study is ReACT's clinical update, assessing long-term sustained efficacy. The ReACT phase IIA/B noncontrolled, open-label, clinical trial enrolled 14 patients with refractory angina and viable ischemic myocardium, without ventricular dysfunction, who were not suitable for myocardial revascularization. The procedure consisted of direct myocardial injection of a specific mononuclear cell formulation, with a certain percentage of promonocytes, in a single series of multiple injections (24-90; 0.2 ml each) into specific areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at the 12-month follow-up and ischemic area reduction (scintigraphic analysis) at the 12-month follow-up, in correlation with ReACT's formulation. A recovery index (for patients with more than 1 year follow-up) was created to evaluate CCSAC over time, until April 2011. Almost all patients presented progressive improvement in CCSAC beginning 3 months (p=0.002) postprocedure, which was sustained at the 12-month follow-up (p=0.002), as well as objective myocardium ischemic area reduction at 6 months (decrease of 15%, p<0.024) and 12 months (decrease of 100%, p<0.004) The recovery index (n=10) showed that the patients were graded less than CCSAC 4 for 73.9 ± 24.2% over a median follow-up time of 46.8 months. After characterization, ReACT's promonocyte concentration suggested a positive correlation with CCSAC improvement (r=-0.575, p=0.082). Quality of life (SF-36 questionnaire) improved significantly in almost all domains. Cost-effectiveness analysis showed decrease in angina-related direct costs. Refractory angina patients presented a sustained long-term improvement in CCSAC and myocardium ischemic areas after the procedure. The long-term follow-up and strong improvement in quality of life reinforce effectiveness. Promonocytes may play a key role in myocardial neoangiogenesis. ReACT dramatically decreased direct costs.