Epigenetic Network in Immunometabolic Disease.

Although a large amount of data consistently shows that genes affect immunometabolic characteristics and outcomes, epigenetic mechanisms are also heavily implicated. Epigenetic changes, including DNA methylation, histone modification, and noncoding RNA, determine gene activity by altering the accessibility of chromatin to transcription factors. Various factors influence these alterations, including genetics, lifestyle, and environmental cues. Moreover, acquired epigenetic signals can be transmitted across generations, thus contributing to early disease traits in the offspring. A closer investigation is critical in this aspect as it can help to understand the underlying molecular mechanisms further and gain insights into potential therapeutic targets for preventing and treating diseases arising from immuno-metabolic dysregulation. In this review, the role of chromatin alterations in the transcriptional modulation of genes involved in insulin resistance, systemic inflammation, macrophage polarization, endothelial dysfunction, metabolic cardiomyopathy, and nonalcoholic fatty liver disease (NAFLD), is discussed. An overview of emerging chromatin-modifying drugs and the importance of the individual epigenetic profile for personalized therapeutic approaches in patients with immuno-metabolic disorders is also presented.

Association between platelet lymphocyte ratio and neutrophil lymphocyte ratio and clinical outcomes following carotid endarterectomy.

Background: Approximately 30% of stroke cases result from carotid disease. Although several risk factors for complications after carotid endarterectomy have been identified, the existence of a biomarker that can estimate postoperative risk in these patients has not yet been proven. Objectives: This study aimed to investigate correlations between the platelet-lymphocyte ratio (PLR) and the neutrophil-lymphocyte ratio (NLR) and postoperative clinical outcomes in patients undergoing carotid endarterectomy. Methods: A retrospective study was conducted, including 374 patients who underwent carotid endarterectomy between 2002 and 2019 due to moderate to high extracranial internal carotid artery stenosis. Their platelet-lymphocyte ratio and neutrophil-lymphocyte ratios were obtained from the same blood samples. Results: There was a statistically significant correlation between the PLR and the occurrence of restenosis (p < 0.01) and acute myocardial infarction (AMI) after endarterectomy (p = 0.03). Additionally, there was a statistically significant correlation between the PLR and the combined outcomes stroke and/or AMI and/or death (p = 0.03) and stroke and/or AMI and/or death and/or restenosis (p < 0.01). However, there were no significant correlations between NLR and these outcomes (p = 0.05, p = 0.16). Conclusions: The platelet-lymphocyte ratio proved to be a useful test for predicting occurrence of strokes, acute myocardial infarctions, and deaths during the postoperative period after carotid endarterectomy. It was also associated with the risk of postoperative restenosis.

Contexto: Aproximadamente 30% dos casos de acidente vascular cerebral (AVC) resultam de doença carotídea. Embora vários fatores de risco para complicações pós-endarterectomia carotídea tenham sido identificados, ainda não foi comprovada a existência de um biomarcador que possa estimar o risco pós-operatório nesses pacientes. Objetivos: Correlacionar o índice plaqueta-linfócito (IPL) e o índice neutrófilo-linfócito (INL) com os desfechos clínicos pós-operatórios em pacientes submetidos a endarterectomia carotídea. Métodos: Estudo retrospectivo que incluiu 374 pacientes submetidos a endarterectomia carotídea, entre 2009 e 2019, por estenose extracraniana da artéria carótida interna. O IPL e o INL foram calculados, tendo sido obtidos das mesmas amostras de sangue. Resultados: Houve correlação estatisticamente significativa entre IPL e presença de reestenose (p<0,01) e infarto agudo do miocárdio (IAM) após endarterectomia (p=0,03). Os desfechos combinados AVC e/ou IAM e/ou óbito e AVC e/ou IAM e/ou óbito e/ou reestenose apresentaram, respectivamente, correlação estatisticamente significativa com o IPL (p=0,03; p<0,01) e não significativa com o INL (p=0,05; p=0,16). Conclusões: O IPL mostrou-se um teste útil, capaz de predizer os desfechos de AVC e/ou IAM e/ou óbito em pacientes no pós-operatório de endarterectomia carotídea, relacionando-se também com risco de reestenose pós-operatória.

Mitochondrial epigenetics in aging and cardiovascular diseases.

Mitochondria are cellular organelles which generate adenosine triphosphate (ATP) molecules for the maintenance of cellular energy through the oxidative phosphorylation. They also regulate a variety of cellular processes including apoptosis and metabolism. Of interest, the inner part of mitochondria-the mitochondrial matrix-contains a circular molecule of DNA (mtDNA) characterised by its own transcriptional machinery. As with genomic DNA, mtDNA may also undergo nucleotide mutations that have been shown to be responsible for mitochondrial dysfunction. During physiological aging, the mitochondrial membrane potential declines and associates with enhanced mitophagy to avoid the accumulation of damaged organelles. Moreover, if the dysfunctional mitochondria are not properly cleared, this could lead to cellular dysfunction and subsequent development of several comorbidities such as cardiovascular diseases (CVDs), diabetes, respiratory and cardiovascular diseases as well as inflammatory disorders and psychiatric diseases. As reported for genomic DNA, mtDNA is also amenable to chemical modifications, namely DNA methylation. Changes in mtDNA methylation have shown to be associated with altered transcriptional programs and mitochondrial dysfunction during aging. In addition, other epigenetic signals have been observed in mitochondria, in particular the interaction between mtDNA methylation and non-coding RNAs. Mitoepigenetic modifications are also involved in the pathogenesis of CVDs where oxygen chain disruption, mitochondrial fission, and ROS formation alter cardiac energy metabolism leading to hypertrophy, hypertension, heart failure and ischemia/reperfusion injury. In the present review, we summarize current evidence on the growing importance of epigenetic changes as modulator of mitochondrial function in aging. A better understanding of the mitochondrial epigenetic landscape may pave the way for personalized therapies to prevent age-related diseases.

Genetic deletion of hepatic NCOR1 protects from atherosclerosis by promoting alternative bile acid-metabolism and sterol excretion.

BACKGROUND: The nuclear receptor corepressor 1 (NCOR1) plays an important role in the regulation of gene expression in immunometabolic conditions by connecting chromatin-modifying enzymes, coregulators and transcription factors. NCOR1 has been shown to be involved in cardiometabolic diseases. Recently, we demonstrated that the deletion of macrophage NCOR1 aggravates atherosclerosis by promoting CD36-triggered foam cell formation via PPARG derepression. PURPOSE: Since NCOR1 modulates the function of several key regulators involved in hepatic lipid and bile acid metabolism, we hypothesized that its deletion in hepatocytes alters lipid metabolism and atherogenesis. METHODS: To test this hypothesis, we generated hepatocyte-specific Ncor1 knockout mice on a Ldlr-/- background. Besides assessing the progression of the disease in thoracoabdominal aortae en face, we analyzed hepatic cholesterol and bile acid metabolism at expression and functional levels. RESULTS: Our data demonstrate that liver-specific Ncor1 knockout mice on an atherosclerosis-prone background develop less atherosclerotic lesions than controls. Interestingly, under chow diet, plasma cholesterol levels of liver-specific Ncor1 knockout mice were slightly higher compared to control, but strongly reduced compared to control mice after feeding them an atherogenic diet for 12 weeks. Moreover, the hepatic cholesterol content was decreased in liver-specific Ncor1 knockout compared to control mice. Our mechanistic data revealed that NCOR1 reprograms the synthesis of bile acids towards the alternative pathway, which in turn reduce bile hydrophobicity and enhances fecal cholesterol excretion. CONCLUSIONS: Our data suggest that hepatic Ncor1 deletion in mice decreases atherosclerosis development by reprograming bile acid metabolism and enhancing fecal cholesterol excretion.

Association between platelet lymphocyte ratio and neutrophil lymphocyte ratio and clinical outcomes following carotid endarterectomy / Associação do índice plaqueta-linfócito e do índice neutrófilo-linfócito com desfechos clínicos após endarterectomia de carótida

Abstract Background Approximately 30% of stroke cases result from carotid disease. Although several risk factors for complications after carotid endarterectomy have been identified, the existence of a biomarker that can estimate postoperative risk in these patients has not yet been proven. Objectives This study aimed to investigate correlations between the platelet-lymphocyte ratio (PLR) and the neutrophil-lymphocyte ratio (NLR) and postoperative clinical outcomes in patients undergoing carotid endarterectomy. Methods A retrospective study was conducted, including 374 patients who underwent carotid endarterectomy between 2002 and 2019 due to moderate to high extracranial internal carotid artery stenosis. Their platelet-lymphocyte ratio and neutrophil-lymphocyte ratios were obtained from the same blood samples. Results There was a statistically significant correlation between the PLR and the occurrence of restenosis (p < 0.01) and acute myocardial infarction (AMI) after endarterectomy (p = 0.03). Additionally, there was a statistically significant correlation between the PLR and the combined outcomes stroke and/or AMI and/or death (p = 0.03) and stroke and/or AMI and/or death and/or restenosis (p < 0.01). However, there were no significant correlations between NLR and these outcomes (p = 0.05, p = 0.16). Conclusions The platelet-lymphocyte ratio proved to be a useful test for predicting occurrence of strokes, acute myocardial infarctions, and deaths during the postoperative period after carotid endarterectomy. It was also associated with the risk of postoperative restenosis.

Resumo Contexto Aproximadamente 30% dos casos de acidente vascular cerebral (AVC) resultam de doença carotídea. Embora vários fatores de risco para complicações pós-endarterectomia carotídea tenham sido identificados, ainda não foi comprovada a existência de um biomarcador que possa estimar o risco pós-operatório nesses pacientes. Objetivos Correlacionar o índice plaqueta-linfócito (IPL) e o índice neutrófilo-linfócito (INL) com os desfechos clínicos pós-operatórios em pacientes submetidos a endarterectomia carotídea. Métodos Estudo retrospectivo que incluiu 374 pacientes submetidos a endarterectomia carotídea, entre 2009 e 2019, por estenose extracraniana da artéria carótida interna. O IPL e o INL foram calculados, tendo sido obtidos das mesmas amostras de sangue. Resultados Houve correlação estatisticamente significativa entre IPL e presença de reestenose (p<0,01) e infarto agudo do miocárdio (IAM) após endarterectomia (p=0,03). Os desfechos combinados AVC e/ou IAM e/ou óbito e AVC e/ou IAM e/ou óbito e/ou reestenose apresentaram, respectivamente, correlação estatisticamente significativa com o IPL (p=0,03; p<0,01) e não significativa com o INL (p=0,05; p=0,16). Conclusões O IPL mostrou-se um teste útil, capaz de predizer os desfechos de AVC e/ou IAM e/ou óbito em pacientes no pós-operatório de endarterectomia carotídea, relacionando-se também com risco de reestenose pós-operatória.

Carotid Plaque Composition and the Importance of Non-Invasive in Imaging Stroke Prevention.

Luminal stenosis has been the standard feature for the current management strategies in patients with atherosclerotic carotid disease. Histological and imaging studies show considerable differences between plaques with identical degrees of stenosis. They indicate that specific plaque characteristics like Intraplaque hemorrhage, Lipid Rich Necrotic Core, Plaque Inflammation, Thickness and Ulceration are responsible for the increased risk of ischemic events. Intraplaque hemorrhage is defined by the accumulation of blood components within the plaque, Lipid Rich Necrotic Core is composed of macrophages loaded with lipid, Plaque Inflammation is defined as the process of atherosclerosis itself and Plaque thickness and Ulceration are defined as morphological features. Advances in imaging methods like Magnetic Resonance Imaging, Ultrasound, Computed Tomography and Positron Emission Tomography have enabled a more detailed characterization of the plaque, and its vulnerability is linked to these characteristics, changing the management of these patients based only on the degree of plaque stenosis. Studies like Rotterdam, ARIC, PARISK, CAPIAS and BIOVASC were essential to evaluate and prove the relevance of these characteristics with cerebrovascular symptoms. A better approach for the prevention of stroke is needed. This review summarizes the more frequent carotid plaque features and the available validation from recent studies with the latest evidence.

Short-Term Outcomes of Transfemoral Carotid Artery Stenting and Carotid Endarterectomy in Symptomatic Patients: Data from a Multicentric Prospective Registry in Brazil.

BACKGROUND: Transfemoral carotid artery stenting (TF-CAS) and carotid endarterectomy (CEA) are alternative strategies for stroke prevention in patients with atherosclerotic carotid disease. Because their main objective is to prevent future ischemic events, regular reassessment of the outcomes is mandatory for providing the best therapy. The purpose of this study was to describe the practice and the outcomes of TF-CAS and CEA in symptomatic patients in public university hospitals in Brazil, using data from a prospective multicentric registry. METHODS: A prospective 8-year observational study of patients with symptomatic carotid artery atherosclerotic disease that underwent TF-CAS and CEA in 5 public university hospitals affiliated with the RHEUNI (Registry Project of Vascular Disease in the Public University Hospitals of São Paulo). All consecutive procedures were included. The indications for the procedures were determined by each surgeon's individual discretion, in accordance with a preoperative risk evaluation. The outcome measures were any 30-day follow-up death, stroke, myocardial infarction (MI), and their combined outcome (major adverse cardiovascular events [MACE]). The registration of the study was made at clinicaltrials.gov NCT02538276. RESULTS: From January 2012 through December 2019, 376 consecutive and symptomatic patients were included in the study records. There were 152 TF-CAS procedures (40.4%) and 224 CEA procedures (59.5%). All completed the 30-day follow-up period. Occurrence of death (TF-CAS: 0.66% × CEA: 0.66%, P = 0.99), stroke (TF-CAS: 4.61% × CEA: 4.46%, P = 0.99), and MI (TF-CAS: 0.66% × CEA: 0%, P = 0.403) were similar in both groups, without statistically significant differences. MACE rate did not differ in both groups (TF-CAS: 5.92% × CEA: 4.46%, P = 0.633). CONCLUSIONS: Data from a prospective registry of 5 Brazilian university hospitals showed that TF-CAS and CEA in symptomatic patients had similar 30-day perioperative rates of death, stroke, and MI and their combination.

Role of the Nuclear Receptor Corepressor 1 (NCOR1) in Atherosclerosis and Associated Immunometabolic Diseases.

Atherosclerotic cardiovascular disease is part of chronic immunometabolic disorders such as type 2 diabetes and nonalcoholic fatty liver disease. Their common risk factors comprise hypertension, insulin resistance, visceral obesity, and dyslipidemias, such as hypercholesterolemia and hypertriglyceridemia, which are part of the metabolic syndrome. Immunometabolic diseases include chronic pathologies that are affected by both metabolic and inflammatory triggers and mediators. Important and challenging questions in this context are to reveal how metabolic triggers and their downstream signaling affect inflammatory processes and vice-versa. Along these lines, specific nuclear receptors sense changes in lipid metabolism and in turn induce downstream inflammatory and metabolic processes. The transcriptional activity of these nuclear receptors is regulated by the nuclear receptor corepressors (NCORs), including NCOR1. In this review we describe the function of NCOR1 as a central immunometabolic regulator and focus on its role in atherosclerosis and associated immunometabolic diseases.

Macrophage NCOR1 protects from atherosclerosis by repressing a pro-atherogenic PPARγ signature.

AIMS: Nuclear receptors and their cofactors regulate key pathophysiological processes in atherosclerosis development. The transcriptional activity of these nuclear receptors is controlled by the nuclear receptor corepressors (NCOR), scaffolding proteins that form the basis of large corepressor complexes. Studies with primary macrophages demonstrated that the deletion of Ncor1 increases the expression of atherosclerotic molecules. However, the role of nuclear receptor corepressors in atherogenesis is unknown. METHODS AND RESULTS: We generated myeloid cell-specific Ncor1 knockout mice and crossbred them with low-density lipoprotein receptor (Ldlr) knockouts to study the role of macrophage NCOR1 in atherosclerosis. We demonstrate that myeloid cell-specific deletion of nuclear receptor corepressor 1 (NCOR1) aggravates atherosclerosis development in mice. Macrophage Ncor1-deficiency leads to increased foam cell formation, enhanced expression of pro-inflammatory cytokines, and atherosclerotic lesions characterized by larger necrotic cores and thinner fibrous caps. The immunometabolic effects of NCOR1 are mediated via suppression of peroxisome proliferator-activated receptor gamma (PPARγ) target genes in mouse and human macrophages, which lead to an enhanced expression of the CD36 scavenger receptor and subsequent increase in oxidized low-density lipoprotein uptake in the absence of NCOR1. Interestingly, in human atherosclerotic plaques, the expression of NCOR1 is reduced whereas the PPARγ signature is increased, and this signature is more pronounced in ruptured compared with non-ruptured carotid plaques. CONCLUSIONS: Our findings show that macrophage NCOR1 blocks the pro-atherogenic functions of PPARγ in atherosclerosis and suggest that stabilizing the NCOR1-PPARγ binding could be a promising strategy to block the pro-atherogenic functions of plaque macrophages and lesion progression in atherosclerotic patients.

Guidelines for superficial venous thrombosis.

Superficial venous thrombosis (SVT) or superficial thrombophlebitis is characterized by thrombi within superficial veins, with partial involvement or occlusion of the lumen and inflammatory reaction along the course of the vein. Clinical diagnosis tends to be straightforward, but supplementary tests and examinations are needed to confirm thrombosis extension and possible thromboembolic complications. SVT can be associated with deep venous thrombosis in 6 to 40% of cases, with asymptomatic pulmonary embolism (PE) in 20 to 33%, and with symptomatic PE in 2 to 13%. Despite the morbidity and complications, there are currently no Brazilian guidelines for SVT. These guidelines cover the most important issues related to SVT definition, terminology, and etiology, and set out recommendations for diagnosis and treatment.

Thoracic aortic aneurysm in a patient with tuberous sclerosis.

Tuberous sclerosis is a genetic disease with autosomal dominant transmission. Its classic presentation comprises epilepsy, mental deficiencies, and sebaceous adenomas. Aneurysms of the aorta can be detected in people with tuberous sclerosis ranging from children a few months old to young adults. We report the case of a young patient diagnosed with a saccular thoracic aortic aneurysm and tuberous sclerosis who was successfully treated using an endovascular approach.

Stability of Propofol (2,6-Diisopropylphenol) in Thermal Desorption Tubes during Air Transport.

The anesthetic propofol and other exhaled organic compounds can be sampled in Tenax sorbent tubes and analyzed by gas chromatography coupled with mass spectrometry. The aim of this study was to evaluate the stability of propofol in Tenax sorbent tubes during overseas shipping. This is relevant for international pharmacokinetic studies on propofol in exhaled air. Tenax sorbent tube propofol samples with concentrations between 10 and 100 ng were prepared by liquid injection and with a calibration gas generator. For each preparation method, one reference set was analyzed immediately after preparation, a second set was stored at room temperature, and a third one was stored refrigerated. The fourth set was sent from Germany by airmail to USA and back. The shipped set of tubes was analyzed when it returned after 55 days elapsed. Then, the room temperature samples and the refrigerated stored samples were also analyzed. To evaluate the stability of propofol in the stored and shipped tubes, we calculated the recovery rates of each sample set. The mean recovery in the stored samples was 101.2% for the liquid preparation and 134.6% for the gaseous preparation at 4°C. At 22°C, the recovery was 96.1% for liquid preparation and 92.1% for gaseous preparation, whereas the shipped samples had a recovery of 85.3% and 111.3%. Thus, the deviation of the shipped samples is within a range of 15%, which is analytically acceptable. However, the individual values show significantly larger deviations of up to -32.1% (liquid) and 30.9% (gaseous). We conclude that storage of propofol on Tenax tubes at room temperature for 55 days is possible to obtain acceptable results. However, it appears that due to severe temperature and pressure variations air shipment of propofol samples in Tenax tubes without cooling shows severe deviations from the initial concentration. Although it was not tested in this study, we assume that refrigerated transport might be necessary to obtain comparable results as in the stored samples.

A Wideband Dielectric Waveguide-Based 160-GHz Radar Target Generator.

The increasing number of radar sensors in commercial and industrial products leads to a growing demand for system functionality tests. Conventional test procedures require expensive anechoic chambers to provide a defined test environment for radar sensors. In this paper, a compact and low cost dielectric waveguide radar target generator for level probing radars is presented. The radar target generator principle is based on a long dielectric waveguide as a one-target scenery. By manipulating the field distribution of the waveguide, a specific reflection of a radar target is generated. Two realistic scenarios for a tank level probing radar are investigated and suitable targets are designed with full wave simulations. Target distances from 13 cm to at least 9 m are realized with an extruded dielectric waveguide with dielectric losses of 2 dB/m at 160 GHz. Low loss (0.5 dB) and low reflection holders are used to fix the waveguide. Due to the dispersion of the dielectric waveguide, a detailed analysis of its impact on frequency-modulated continuous wave (FMCW) radars is given and compared to free-space propagation. The functionality of the radar target generator is verified with a 160-GHz FMCW radar prototype.

Primary stenting for femoropopliteal peripheral arterial disease: analysis up to 24 months.

BACKGROUND: Primary stenting is a well-established treatment option for femoropopliteal arterial obstructive disease. There is a shortage of Brazilian studies of the subject. OBJECTIVES: To evaluate short and mid-term clinical and radiological outcomes in patients classified as Rutherford 3-6 and treated with stenting of femoropopliteal lesions. METHODS: Analysis based on a prospectively populated database of patients treated from July 2012 to July 2015. The primary endpoint was primary patency. Secondary endpoints were clinical and ankle/brachial index changes. Target Vessel Revascularization, limb salvage rate and death, within a 24-month follow-up period. RESULTS: 64 patients were enrolled, including 61 TASC II A / B lesions (95%). The primary patency rates at 6, 12, and 24 months were 95.2%, 79.1% and 57.9%, respectively. Cox regression analysis revealed lower patency rates in patients with occlusive disease (hazard ratio [HR], 6.64; 95% confidence interval [CI], 1.52-28,99, p = 0.02), as well as patency loss about 6 times higher in TASC B than in TASC A patients ([HR], 5.95, 95% CI, 1.67-21.3, p = 0.0061). At 12 months, 90.38% of the patients remained asymptomatic. The limb salvage rate at 24 months was 94.3% (95% CI, 87.9-100%). Freedom from TVR at 24 months was 90.5% (95% CI 82.8-98.9%). CONCLUSIONS: Results of primary patency were compatible with international studies, despite the more advanced stage of the vascular disease observed in our group. Occlusive disease and complex lesions were both associated with worse outcomes.

Tratamento da doença arterial obstrutiva periférica em território femoropoplíteo com stent primário: análise em até 24 meses / Primary stenting for femoropopliteal peripheral arterial disease: analysis up to 24 months

O stent primário é uma opção de tratamento bem estabelecida para a doença arterial periférica em território femoropoplíteo. Estudos nacionais são escassos. Objetivos Avaliar desfechos clínicos e radiológicos em curto e médio prazo em pacientes classificados como Rutherford 3-6, tratados com o uso de stent em lesões femoropoplíteas. Métodos A análise foi realizada com base em um banco de dados prospectivamente mantido de doentes tratados entre julho de 2012 e julho de 2015. O objetivo primário foi a perviedade. Os objetivos secundários foram melhora na classificação de Rutherford, índice tornozelo/braço, revascularização do vaso-alvo, taxa de salvamento do membro e óbito em até 24 meses. Resultados Foram incluídos 64 pacientes, sendo 61 com lesões TASC II A/B (95%). A taxa de perviedade primária em 6, 12 e 24 meses foi de 95,2%, 79,1% e 57,9%, respectivamente. A análise de regressão de Cox revelou uma menor perviedade em pacientes com doença oclusiva (RR, 6,64, IC 95%, 1,52-28,99, p = 0,02), bem como uma perda de perviedade cerca de seis vezes maior em doentes TASC B do que TASC A (RR, 5,95, IC 95%, 1,67-21,3, p = 0,0061). Em 12 meses, 90,38% dos doentes permaneceram assintomáticos. A taxa de salvamento do membro em 24 meses foi de 94,3% (IC 95%, 87,9-100%). A ausência de revascularização do vaso-alvo em 24 meses foi de 90,5% (IC 95%, 82,8-98,9%). Conclusões Os resultados foram compatíveis com estudos internacionais, apesar do estágio mais avançado da doença vascular observada em nosso grupo. Piores desfechos foram associados a doença oclusiva e lesões complexas

Primary stenting is a well-established treatment option for femoropopliteal arterial obstructive disease. There is a shortage of Brazilian studies of the subject. Objectives To evaluate short and mid-term clinical and radiological outcomes in patients classified as Rutherford 3-6 and treated with stenting of femoropopliteal lesions. Methods Analysis based on a prospectively populated database of patients treated from July 2012 to July 2015. The primary endpoint was primary patency. Secondary endpoints were clinical and ankle/brachial index changes. Target Vessel Revascularization, limb salvage rate and death, within a 24-month follow-up period. Results 64 patients were enrolled, including 61 TASC II A / B lesions (95%). The primary patency rates at 6, 12, and 24 months were 95.2%, 79.1% and 57.9%, respectively. Cox regression analysis revealed lower patency rates in patients with occlusive disease (hazard ratio [HR], 6.64; 95% confidence interval [CI], 1.52-28,99, p = 0.02), as well as patency loss about 6 times higher in TASC B than in TASC A patients ([HR], 5.95, 95% CI, 1.67-21.3, p = 0.0061). At 12 months, 90.38% of the patients remained asymptomatic. The limb salvage rate at 24 months was 94.3% (95% CI, 87.9-100%). Freedom from TVR at 24 months was 90.5% (95% CI 82.8-98.9%). Conclusions Results of primary patency were compatible with international studies, despite the more advanced stage of the vascular disease observed in our group. Occlusive disease and complex lesions were both associated with worse outcomes

Aneurisma de aorta torácica em paciente com esclerose tuberosa / Thoracic aortic aneurysm in a patient with tuberous sclerosis

A esclerose tuberosa é uma doença genética de transmissão autossômica dominante. Caracteriza-se, na sua apresentação clássica, por epilepsia, deficiência mental e adenomas sebáceos. Aneurismas de aorta podem acometer desde crianças com poucos meses de vida até adultos jovens portadores de esclerose tuberosa. Apresentamos o caso de uma paciente jovem com diagnóstico de aneurisma sacular de aorta torácica e esclerose tuberosa tratada com sucesso por via endovascular

Tuberous sclerosis is a genetic disease with autosomal dominant transmission. Its classic presentation comprises epilepsy, mental deficiencies, and sebaceous adenomas. Aneurysms of the aorta can be detected in people with tuberous sclerosis ranging from children a few months old to young adults. We report the case of a young patient diagnosed with a saccular thoracic aortic aneurysm and tuberous sclerosis who was successfully treated using an endovascular approach

Parallelized Monte Carlo software to efficiently simulate the light propagation in arbitrarily shaped objects and aligned scattering media.

A GPU-based Monte Carlo software (MCtet) was developed to calculate the light propagation in arbitrarily shaped objects, like a human tooth, represented by a tetrahedral mesh. A unique feature of MCtet is a concept to realize different kinds of light-sources illuminating the complex-shaped surface of an object, for which no preprocessing step is needed. With this concept, it is also possible to consider photons leaving a turbid media and reentering again in case of a concave object. The correct implementation was shown by comparison with five other Monte Carlo software packages. A hundredfold acceleration compared with central processing units-based programs was found. MCtet can simulate anisotropic light propagation, e.g., by accounting for scattering at cylindrical structures. The important influence of the anisotropic light propagation, caused, e.g., by the tubules in human dentin, is shown for the transmission spectrum through a tooth. It was found that the sensitivity to a change in the oxygen saturation inside the pulp for transmission spectra is much larger if the tubules are considered. Another "light guiding" effect based on a combination of a low scattering and a high refractive index in enamel is described.

Novel Method for Superposing 3D Digital Models for Monitoring Orthodontic Tooth Movement.

Quantitative three-dimensional analysis of orthodontic tooth movement (OTM) is possible by superposition of digital jaw models made at different times during treatment. Conventional methods rely on surface alignment at palatal soft-tissue areas, which is applicable to the maxilla only. We introduce two novel numerical methods applicable to both maxilla and mandible. The OTM from the initial phase of multi-bracket appliance treatment of ten pairs of maxillary models were evaluated and compared with four conventional methods. The median range of deviation of OTM for three users was 13-72% smaller for the novel methods than for the conventional methods, indicating greater inter-observer agreement. Total tooth translation and rotation were significantly different (ANOVA, p < 0.01) for OTM determined by use of the two numerical and four conventional methods. Directional decomposition of OTM from the novel methods showed clinically acceptable agreement with reference results except for vertical translations (deviations of medians greater than 0.6 mm). The difference in vertical translational OTM can be explained by maxillary vertical growth during the observation period, which is additionally recorded by conventional methods. The novel approaches are, thus, particularly suitable for evaluation of pure treatment effects, because growth-related changes are ignored.

Calibration and validation of a MCC/IMS prototype for exhaled propofol online measurement.

Propofol is a commonly used intravenous general anesthetic. Multi-capillary column (MCC) coupled Ion-mobility spectrometry (IMS) can be used to quantify exhaled propofol, and thus estimate plasma drug concentration. Here, we present results of the calibration and analytical validation of a MCC/IMS pre-market prototype for propofol quantification in exhaled air. Calibration with a reference gas generator yielded an R2≥0.99 with a linear array for the calibration curve from 0 to 20 ppbv. The limit of quantification was 0.3 ppbv and the limit of detection was 0.1 ppbv. The device is able to distinguish concentration differences >0.5 ppbv for the concentration range between 2 and 4 ppbv and >0.9 ppbv for the range between 28 and 30 ppbv. The imprecision at 20 ppbv is 11.3% whereas it is 3.5% at a concentration of 40 ppbv. The carry-over duration is 3min. The MCC/IMS we tested provided online quantification of gaseous propofol over the clinically relevant range at measurement frequencies of one measurement each minute.