Atherosclerosis and Bone Loss in Humans-Results From Deceased Donors and From Patients Submitted to Carotid Endarterectomy.

Background and Aims: Atherosclerosis and osteoporosis share common risk factors, as well as inflammatory mechanisms. Our aim was to understand how atherosclerotic lesions are related with disturbances in bone. Methods: Gene expression of pro-inflammatory and bone metabolism related proteins (IL-1ß, IL-6, IL-17A, TNF, RANKL, OPG, COL1, CTSK, OCL, TRAP, CBFA1, DKK1, SOST, ADIPOQ, and ADIPOR1) were analyzed in arteries and bones from 45 deceased donors and adipose tissue was used as control. Additionally, in 139 patients with advanced atherosclerosis submitted to carotid endarterectomy we compared calcium content (Alizarin red) and plaque inflammatory scores (CD3+, CD68+, and adiponectin) of patients with normal bone mineral density (BMD) with those with low BMD and explored the associations between gene expression in atherosclerotic plaques and BMD. Serum levels of pro-inflammatory and bone related proteins were measured both in donors and patients. Associations were investigated by the Pearson or Spearman correlation tests, and multivariate regression analyzes were performed when justified. Results: Gene expression of bone remodeling and pro-inflammatory proteins correlated positively in bone and aorta, independently of age and sex of donors, but not in adipose tissue. The expression of bone formation genes was significantly higher in atheroma plaques from endarterectomized patients with normal vs. low BMD as well as inflammatory CD68+ scores, regardless of patients' age and sex, but not of body mass index. No relationship was observed between serum levels and gene expression levels of pro-inflammatory or bone remodeling proteins. Conclusions: Our results suggest that the relationship between bones and vessels in the context of atherosclerotic disease and osteoporosis may rely on the intrinsic connection between the tissues involved, independently of disease stage. Serum measurements of pro-inflammatory and bone-remodeling proteins do not accurately translate tissue pathologic processes.

Fluoroquinolones Are Associated With Increased Risk of Aortic Aneurysm or Dissection: Systematic Review and Meta-analysis.

Fluoroquinolone use has been associated with collagen disease events, raising safety concerns. We hypothesized that the use of fluoroquinolones is associated with aortic aneurysm (AA) and aortic dissection or aortic rupture (AD/AR). We performed a systematic review with meta-analysis on studies published until March 2019. Seven observational studies were included, comprising 2,851,646 participants. The studies were evaluated regarding their risk of bias. Results on fluoroquinolone use risk comparing with nontreatment and with beta-lactam antibiotic use were extracted. The estimates were pooled through a random-effects model meta-analysis and heterogeneity assessed through the I2 statistic. Sensitivity analysis were performed, grouping studies per design and with exclusion of studies with critical risk of bias. Fluoroquinolone use was associated with a higher risk of AA/AD/AR, comparing with a nontreatment intervention (odds ratio = 2.26; 95%CI 1.93-2.65; I2 = 30%) and comparing with a beta-lactam intervention (odds ratio = 1.56; 95%CI 1.37-1.79; I2 = 0%). This harm effect remained significant when pooling the results for the AD/AR outcome only and across various study designs. Studies comparing with beta-lactam intervention were considered to have a moderate risk of bias, while the remaining ones were classified as having at least a serious risk of bias. All evaluated outcomes had very low Grading of Recommendation, Assessment, Development and Evaluation evidence. Fluoroquinolone use was associated with a significant risk of AA/AD/AR.

Aortic Dissection Repair Using the STABILISE Technique Associated with Arch Procedures: Report of Two Cases.

INTRODUCTION: The stent assisted balloon induced intimal disruption and relamination in aortic dissection repair (STABILISE) technique is being increasingly used for the treatment of complicated aortic dissections. However, as it is a fairly recent technique, the scientific information is limited. REPORT: In this paper we report two cases of the STABILISE technique associated with procedures in the ascending aorta and supra-aortic trunks, consisting of a "frozen elephant trunk" procedure in one case and in the other, a carotid endarterectomy associated with reimplantation of the vertebral artery and partial arch debranching. DISCUSSION: In conclusion, while acknowledging the need for longer follow up and greater experience to support the safety and efficacy of this procedure, the two cases reported confirm that the STABILISE technique is a valid endovascular alternative in the treatment of complicated aortic dissections.

An ultrasonographic risk score for detecting symptomatic carotid atherosclerotic plaques.

this paper proposes a risk score computed from ultrasound data that correlates to plaque activity. It has the twofold purpose of detecting symptomatic plaques and estimating the likelihood of the asymptomatic lesion to become symptomatic. The proposed ultrasonographic activity index (UAI) relies on the plaque active profile, which is a combination of the most discriminate ultrasound parameter associated with symptoms. These features are extracted by the automatic algorithm and also by the physician from the ultrasound images and from some transformations on it, such as monogenic decomposition, which is a novelty in this clinical problem. This information is used to compute a risk score from the conditional probabilities of either symptomatic or asymptomatic groups. Symptom detection performance is evaluated on a transversal dataset of 146 plaques, where UAI obtained 83.5% accuracy, 84.1% sensitivity, and 83.7% specificity. Performance is also assessed on a longitudinal study of 112 plaques, where UAI shows a significant improvement over the gold standard degree of stenosis, demonstrating higher power at predicting which asymptomatic plaques developed symptoms in an average follow-up of ten months. Results suggest that this score could have a positive impact on early stroke prevention and treatment planning.

Asymptomatic carotid disease--a new tool for assessing neurological risk.

Active carotid plaques are associated with atheroembolism and neurological events; its identification is crucial for stroke prevention. High-definition ultrasound (HDU) can be used to recognize plaque structure in carotid bifurcation stenosis associated with plaque vulnerability and occurrence of brain ischemic events. A new computer-assisted HDU method to study the echomorphology of the carotid plaque and to determine a risk score for developing appropriate symptoms is proposed in this study. Plaque echomorphology characteristics such as presence of ulceration at the plaque surface, juxta-luminal location of echolucent areas, echoheterogeneity were obtained from B-mode ultrasound scans using several image processing algorithms and were combined with measurement of severity of stenosis to obtain a clinical score--enhanced activity index (EAI)--which was correlated with the presence or absence of ipsilateral appropriate ischemic symptoms. An optimal cutoff value of EAI was determined to obtain the best separation between symptomatic (active) from asymptomatic (inactive) plaques and its diagnostic yield was compared to other 2 reference methods by means of receiver-operating characteristic (ROC) analysis. Classification performance was evaluated by leave-one-patient-out cross-validation applied to a cohort of 146 carotid plaques from 99 patients. The proposed method was benchmarked against (a) degree of stenosis criteria and (b) earlier proposed activity index (AI) and demonstrated that EAI yielded the highest accuracy up to an accuracy of 77% to predict asymptomatic plaques that developed symptoms in a prospective cross-sectional study. Enhanced activity index is a noninvasive, easy to obtain parameter, which provided accurate estimation of neurological risk of carotid plaques.

Mobile health platform for pressure ulcer monitoring with electronic health record integration.

Pressure ulcers frequently occur in patients with limited mobility, for example, people with advanced age and patients wearing casts or prostheses. Mobile information communication technologies can help implement ulcer care protocols and the monitoring of patients with high risk, thus preventing or improving these conditions. This article presents a mobile pressure ulcer monitoring platform (mULCER), which helps control a patient's ulcer status during all stages of treatment. Beside its stand-alone version, it can be integrated with electronic health record systems as mULCER synchronizes ulcer data with any electronic health record system using HL7 standards. It serves as a tool to integrate nursing care among hospital departments and institutions. mULCER was experimented with in different mobile devices such as LG Optimus One P500, Samsung Galaxy Tab, HTC Magic, Samsung Galaxy S, and Samsung Galaxy i5700, taking into account the user's experience of different screen sizes and processing characteristics.

[Sequential surgical treatment of multiple primary infectious aneurysms of the thoracic and abdominal aorta]. / Tratamento cirúrgico sequencial de múltiplos aneurismas infecciosos primários da aorta torácica e abdominal.

A 26-year-old woman, complained of repeated urinary infections at the beginning of February 2010. Several urine sample tests identified an Escherichia colli strain, which was treated with antibiotics, according to the antibiogram data. Shortly afterwards, as a result of a back pain, a pyelonephritis was diagnosed, which was also treated with antibiotics. The pain progressively intensified over time and in June 2011 she began to suffer from high and persistent fever, which led to her hospitalisation. The investigation through CT-angiography showed the existence of three aneurysms of the thoracic aorta (one of the aortic arch and two of the descending thoracic aorta) and a large aneurysm of the abdominal aorta, in a contained rupture, surrounding the origin of the renal arteries, of infectious etiology. The patient underwent three sequential and successful surgical operations, using the conventional approach that consisted in the resection and replacement of the aneurysms with "in situ" vascular prosthesis. The main aspects of the pathology, clinical presentation and treatment of this extensive, rare and challenging situation are presented and discussed herein.

[Surgical management of a congenital abdominal aortic coarctation, associated to renal and mesenteric arteries critical stenosis in a 12-years old young boy]. / Tratamento cirúrgico de uma coartação congénita da aorta abdominal associada a patologia obstrutiva das artérias digestivas e renais, num jovem de 12 anos de idade.

The clinical case of a 12-years old boy complaining of severe and refractory arterial hypertension is reported, in whom an angio-CT evaluation displayed the diagnosis of a congenital abdominal aortic coarctation, associated to a critical stenosis of both renal and superior mesenteric arteries. The patient underwent a complex revascularization procedure, consisting in the implantation of an aorto-aortic bypass graft, followed by both renals and superior mesenteric artery revascularization. The post-operative course was uneventful and blood pressure turned down immediately to normal values. A post-operative angio-CT control revealed the anatomic and functional integrity of the surgical revascularization procedure. The main features of pathology, clinical presentation, diagnosis and surgical management of this exceedingly rare condition are subjected to a discussion, based on an extensive review of the literature published on the topic.

Activator protein-1 in carotid plaques is related to cerebrovascular symptoms and cholesteryl ester content.

INTRODUCTION: Transcription factor activator protein-1 regulates genes involved in inflammation and repair. The aim of this study was to determine whether transcription factor activator protein-1 activity in carotid plaques is related to symptoms, lipid accumulation, or extracellular matrix composition. METHODS: Twenty-eight atherosclerotic carotid plaques were removed by endarterectomy and divided into two groups based on the presence or absence of ipsilateral symptoms (<1 month ago). Activator protein-1 DNA binding activity was assessed, and subunit (c-Jun, JunD, JunB, c-Fos, FosB, Fra-1, Fra-2) protein levels analyzed by immunoblotting. Distribution of c-Jun in plaques was analyzed by immunohistochemistry. RESULTS: Plaques associated with symptoms had increased activator protein-1 activity and increased expression of c-Jun and JunD, as compared to asymptomatic plaques. Fra-1 and Fra-2 were present in equal amounts in both groups, whereas JunB, FosB, and c-Fos were undetectable. Activator protein-1 activity correlated with cholesteryl ester and elastin in plaques and decreased with age. Activator protein-1 activity did not correlate with collagen, calcified tissue, or proteoglycan content. CONCLUSIONS: Activator protein-1 is increased in plaques associated with symptoms. The correlation between activator protein-1 and cholesteryl esters suggests that high activator protein-1 is a marker of plaque vulnerability. Activator protein-1 expression can also reflect the activation of repair processes.

Activation of calpain-1 in human carotid artery atherosclerotic lesions.

BACKGROUND: In a previous study, we observed that oxidized low-density lipoprotein-induced death of endothelial cells was calpain-1-dependent. The purpose of the present paper was to study the possible activation of calpain in human carotid plaques, and to compare calpain activity in the plaques from symptomatic patients with those obtained from patients without symptoms. METHODS: Human atherosclerotic carotid plaques (n = 29, 12 associated with symptoms) were removed by endarterectomy. Calpain activity and apoptosis were detected by performing immunohistochemical analysis and TUNEL assay on human carotid plaque sections. An antibody specific for calpain-proteolyzed alpha-fodrin was used on western blots. RESULTS: We found that calpain was activated in all the plaques and calpain activity colocalized with apoptotic cell death. Our observation of autoproteolytic cleavage of the 80 kDa subunit of calpain-1 provided further evidence for enzyme activity in the plaque samples. When calpain activity was quantified, we found that plaques from symptomatic patients displayed significantly lower calpain activity compared with asymptomatic plaques. CONCLUSION: These novel results suggest that calpain-1 is commonly active in carotid artery atherosclerotic plaques, and that calpain activity is colocalized with cell death and inversely associated with symptoms.

A 3-D ultrasound-based framework to characterize the echo morphology of carotid plaques.

Carotid atherosclerosis is the main cause of brain stroke, which is the most common life-threatening neurological disease. Nearly all methods aiming at assessing the risk of plaque rupture are based on its characterization from 2-D ultrasound images, which depends on plaque geometry, degree of stenosis, and echo morphology (intensity and texture). The computation of these indicators is, however, usually affected by inaccuracy and subjectivity associated with data acquisition and operator-dependent image selection. To circumvent these limitations, a novel and simple method based on 3-D freehand ultrasound is proposed that does not require any expensive equipment except the common scanner. This method comprises the 3-D reconstruction of carotids and plaques to provide clinically meaningful parameters not available in 2-D ultrasound imaging, namely diagnostic views not usually accessible via conventional techniques and local 3-D characterization of plaque echo morphology. The labeling procedure, based on graph cuts, allows us to identify, locate, and quantify potentially vulnerable foci within the plaque. Validation of the characterization method was made with synthetic data. Results of plaque characterization with real data are encouraging and consistent with the results from conventional methods and after inspection of surgically removed plaques.

[Reconstructive surgery of an upper abdominal aortic coarctation, associated to bilateral renal artery aneurysms. Case report]. / Cirurgia reconstructiva de uma coartação da aorta abdominal alta, associada a aneurisma da artéria renal bilateral. Caso clínico.

The authors report the clinical case of a 13 year old girl with the diagnosis of arterial hypertension, consequence of an upper abdominal aortic coarctation, involving the origin of both renal arteries and the superior mesenteric artery. Surgical exploration disclosed the coexistence of displasic aneurysms at the origin of both renal arteries. She underwent a complex revascularization procedure, which is described, and the post operative course was uneventfull, having normalised the values of the blood pressure. The main features of etiopathogeny, clinical presentation, diagnosis and surgical management of this entity are discussed, based on an extensive review of the literature.

[Splenic infarction caused by supra-celiac aortic thrombus. Two case reports]. / Embolia espléinica causada por trombo mural supracelíaca. A propósito de dois casos clínicos.

Aortic mural thrombosis is a rare situation in clinical practice. Its pathogeny is ignored in the majority of cases and clinical presentation is variable, according to the location of the thrombus and the multiple and diverse forms of embolism that can cause. For these reasons, clinical diagnosis may be extremally difficult. The authors report the cases of two women aged 52 and 41 years old respectivelly admitted in the Emergency Department with abdominal and lumbar pain, due splenic embolic infarctions, a diagnosis made by CT-Scans. The computed tomography disclosed also the presence of mural thrombus in the celiac aorta, one of them as a floating thrombus, which were regarded as the source of the embolism. Supraceliac aortic thrombectomy was performed, associated to splenectomy in both cases. Post operative course was uneventfull and reviewed 10 months and 9 years after the operation, they were found in pretty good condition, with no evidence of recurrence of the disease.

Elastin- and collagen-rich human carotid plaques have increased levels of the cysteine protease inhibitor cystatin C.

BACKGROUND: Cystatin C is a major inhibitor of the elastin- and collagen-degrading cysteine proteases and may therefore have an important role in preserving atherosclerotic plaque stability. In this study we analyzed the associations between human carotid plaque cystatin C expression and the plaque content of collagen and elastin. METHODS: Thirty-one plaques were removed by endarterectomy and homogenized. Cystatin C levels were analyzed by densitometry of Western blots and elastin and collagen levels were determined colorimetrically. RESULTS: The plaque content of cystatin C correlated with total elastin (r = 0.58, p = 0.001) and collagen (r = 0.50, p = 0.004), as well as with cross-linked forms of elastin (r = 0.42, p = 0.022) and collagen (r = 0.52, p = 0.003). Immunohistochemical analysis demonstrated that cystatin C colocalized with elastin and collagen. No correlation was seen between cystatin C and the amount of degraded elastin or collagen in plaques. CONCLUSION: The positive correlation between cystatin C levels and collagen and elastin levels in plaques supports the notion that cystatin C plays an important role in maintaining atherosclerotic plaque stability.

Elastin and calcium rather than collagen or lipid content are associated with echogenicity of human carotid plaques.

BACKGROUND AND PURPOSE: Echolucent carotid plaques have been associated with increased risk for stroke. Histological studies suggested that echolucent plaques are hemorrhage- and lipid-rich, whereas echogenic plaques are characterized by fibrosis and calcification. This is the first study to relate echogenicity to plaque composition analyzed biochemically. METHODS: Echogenicity of human carotid plaques was analyzed by standardized high-definition ultrasound and classified into echolucent, with gray-scale median (GSM) <32 and echogenic with GSM > or =32. The biochemical composition of the plaques was assessed by fast-performance liquid chromotography and high-performance thin-layer chromotography. RESULTS: As assessed biochemically (milligrams per gram [mg/g]), echolucent plaques contained less hydroxyapatite (43.8 [SD 41.2] mg/g versus 121.6 [SD 106.2] mg/g; P=0.018), more total elastin (1.7 [SD 0.4] mg/g versus 1.2 [SD 0.4] mg/g; P=0.008), and more intermediate-size elastin forms (1.2 [SD 0.3] mg/g versus 0.8 [SD 0.4] mg/g; P=0.018). There was no difference in collagen amount between echogenic and echolucent plaques, neither biochemically (15.3 [SD 3.7] mg/g versus 14.4 [SD 3.4] mg/g) nor histologically (13.4 [SD 4.9] % versus 13.0 [SD 5.6] %). Cholesterol esters, unesterified cholesterol, and triglycerides were increased in plaques associated with symptoms (22.5 [SD 23.3] mg/g versus 13.3 [SD 3.2]; P=0.04), but no differences were detected between echolucent and echogenic plaques (13.5 [SD 4.0] versus 20.2 [SD 21.5] mg/g). Similar results were obtained by Oil Red O staining (symptomatic 7.6 [SD 4.7] % versus asymptomatic 4.2 [SD 3.6] %; P=0.03; echolucent 5.9 [SD 4.1] % versus echogenic 5.0 [SD 4.0] % of area). CONCLUSIONS: Echogenicity of carotid plaques is mainly determined by their elastin and calcium but not collagen or lipid content. In addition, echolucency is associated to higher elastin content.

Changes related to age and cerebrovascular symptoms in the extracellular matrix of human carotid plaques.

BACKGROUND AND PURPOSE: Many processes involved in the pathogenesis of atherosclerosis result in modifications of the extracellular matrix. These changes not only determine the mechanical stability of atherosclerotic lesions but can directly or indirectly influence further development of the lesions. The purpose of the present study was to compare the matrix composition of human carotid plaques from symptomatic patients with those obtained from patients without symptoms. Furthermore, matrix changes related to age were studied. METHODS: Thirty atherosclerotic carotid plaques were removed by endarterectomy from 27 patients and divided into 2 groups on the basis of the presence of ipsilateral symptoms. The plaques were homogenized, and the total levels of the major components of the extracellular matrix were determined. RESULTS: Plaques associated with symptoms were characterized by increased levels of elastin (1.58+/-0.46 versus 1.24+/-0.40 mg/g wet wt; P=0.03) and decreased levels of hydroxyapatite (45.1+/-46.3 versus 131.4+/-111.7 mg/g wet wt; P=0.02) compared with asymptomatic plaques. The increase in elastin in plaques from symptomatic patients was due to elevated levels of an intermediate-size fraction, as determined by liquid chromatography. Collagen and sulfated glycosaminoglycans were present in equal amounts in both groups. Elastin content in carotid plaques decreased with age. CONCLUSIONS: Carotid plaques from symptomatic patients have lower levels of hydroxyapatite than those from asymptomatic patients. The present study also raises the possibility that non-cross-linked forms of elastin, increased in plaques associated with symptoms, could be a marker of plaque vulnerability and/or directly induce harmful cellular activities or increase lipoprotein retention in the vascular wall.

[Penetrating ulcers of the descending thoracic aorta: Diagnosis and surgical management].

In this paper two patients with penetrating ulcers of the descending thoracic aorta are presented, a clinical condition recognized only recently, that may have a severe or even fatal outcome, due to rupture of the aorta. It is a peculiar form of the atherosclerotic disease, and its clinical and imagiologic presentation may mimics the classic aortic dissection of the distal type type. Computed tomography, nuclear magnetic resonance and transesophageal ecocardiography are the most apropriate methods for studying and diagnosis and the surgical management, aimed at the prevention or treatment of the aortic rupture, and based on the prosthetic aortic replacement, is the only alternative allowing the definite cure of the disease. The main features of pathology, clinical manifestations, diferential diagnosis and surgical management of this entity are described and discussed, according to the most recently articles published in the literature, on the subject.