Vascular smooth muscle cells in atherosclerosis: time for a re-assessment.

Vascular smooth muscle cells (VSMCs) are key participants in both early and late-stage atherosclerosis. VSMCs invade the early atherosclerotic lesion from the media, expanding lesions, but also forming a protective fibrous cap rich in extracellular matrix to cover the 'necrotic' core. Hence, VSMCs have been viewed as plaque-stabilizing, and decreased VSMC plaque content-often measured by expression of contractile markers-associated with increased plaque vulnerability. However, the emergence of lineage-tracing and transcriptomic studies has demonstrated that VSMCs comprise a much larger proportion of atherosclerotic plaques than originally thought, demonstrate multiple different phenotypes in vivo, and have roles that might be detrimental. VSMCs down-regulate contractile markers during atherosclerosis whilst adopting alternative phenotypes, including macrophage-like, foam cell-like, osteochondrogenic-like, myofibroblast-like, and mesenchymal stem cell-like. VSMC phenotypic switching can be studied in tissue culture, but also now in the media, fibrous cap and deep-core region, and markedly affects plaque formation and markers of stability. In this review, we describe the different VSMC plaque phenotypes and their presumed cellular and paracrine functions, the regulatory mechanisms that control VSMC plasticity, and their impact on atherogenesis and plaque stability.

From CT to artificial intelligence for complex assessment of plaque-associated risk.

The recent technological developments in the field of cardiac imaging have established coronary computed tomography angiography (CCTA) as a first-line diagnostic tool in patients with suspected coronary artery disease (CAD). CCTA offers robust information on the overall coronary circulation and luminal stenosis, also providing the ability to assess the composition, morphology, and vulnerability of atherosclerotic plaques. In addition, the perivascular adipose tissue (PVAT) has recently emerged as a marker of increased cardiovascular risk. The addition of PVAT quantification to standard CCTA imaging may provide the ability to extract information on local inflammation, for an individualized approach in coronary risk stratification. The development of image post-processing tools over the past several years allowed CCTA to provide a significant amount of data that can be incorporated into machine learning (ML) applications. ML algorithms that use radiomic features extracted from CCTA are still at an early stage. However, the recent development of artificial intelligence will probably bring major changes in the way we integrate clinical, biological, and imaging information, for a complex risk stratification and individualized therapeutic decision making in patients with CAD. This review aims to present the current evidence on the complex role of CCTA in the detection and quantification of vulnerable plaques and the associated coronary inflammation, also describing the most recent developments in the radiomics-based machine learning approach for complex assessment of plaque-associated risk.

Spontaneous Pneumothorax After Rupture of the Cavity as the Initial Presentation of Tuberculosis in the Emergency Department.

BACKGROUND Spontaneous pneumothorax can be secondary to a wide variety of lung diseases. Spontaneous pneumothorax secondary to pulmonary tuberculosis occurs in rare cases of residual fibrosis with retractions and bullae. CASE REPORT We present the case of a 65-year-old male patient from a rural area in the province of Los Ríos in Babahoyo, Ecuador, with no history of contact with tuberculosis. The patient arrived at the Emergency Department of the Regional Hospital of the Instituto Ecuatoriano de Seguridad Social (IESS), Babahoyo, due to acute respiratory failure, preceded by 10 days of evolution due to cough accompanied by greenish expectoration, chest pain, asthenia, and weight loss. On chest radiography, a left pneumothorax and interstitial pulmonary infiltrate were reported. A chest tube was placed, and the patient was intubated and was placed on invasive mechanical ventilation due to severe respiratory failure. Use of the GeneXpert MTB/RIF System detected Mycobacterium tuberculosis without resistance to rifampicin. Ziehl-Neelsen (ZN) staining for the identification of bacillus acid-resistant alcohol was positive in alveolar bronchial lavage. MALDI-TOF mass spectrometry and phenotypic analysis showed the presence of Pseudomonas aeruginosa and Klebsiella pneumonia with carbapenemases resistance mechanism, and the KPC type enzyme was identified. The culture for Mycobacterium tuberculosis was positive from the fourth week. CONCLUSIONS Secondary pneumothorax due to rupture of the polymicrobial cavity and especially of tuberculous origin is a very special form of acute respiratory failure in patients with previous structural pulmonary lesions in the Emergency Department.

Melatonin inhibits macrophage infiltration and promotes plaque stabilization by upregulating anti-inflammatory HGF/c-Met system in the atherosclerotic rabbit: USPIO-enhanced MRI assessment.

Macrophage plays critical roles in the pathogenesis of atherosclerosis (AS), and is an attractive target for detecting and treating vulnerable plaque. Our previous study showed that melatonin (MLT) ameliorated AS by suppressing the pro-inflammatory Toll-like receptor 4/nuclear factor kappa B system in high-fat-fed rabbit. However, it is unknown whether the anti-atherosclerotic properties of MLT are associated with the upregulation of anti-inflammatory hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-Met) system. In present study, we examined whether MLT could inhibit macrophage infiltration and promote plaque stabilization by upregulating HGF/c-Met system with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) assessment in AS rabbit. Rabbits in this study were randomly divided into three groups and treated with a standard diet, high-fat diet, and high-fat diet plus 10 mg/kg/day MLT for 12 weeks, respectively. MLT treatment significantly reversed spotty signal void in 3D-TOF MRI, standard signal intensity reduction in T2WI MRI and aortic luminal area reduction in 2D-TOF MRI of the atherosclerotic abdominal aorta 72 h after USPIO injection. It also decreased serum interleukin-6 (IL-6), intima/media thickness ratio of the abdominal aorta, CD68 and iron-positive areas in the aortic intima, and increased serum IL-10, HGF and c-Met protein expression and the accumulation of vascular smooth muscle cell and collagen fiber in the aortic intima of AS rabbit. Our data demonstrated that MLT significantly decreased plaque macrophage infiltration and promoted plaque stability in AS rabbit assessed by USPIO-enhanced MRI. Remarkably, it was very first revealed that upregulation of anti-inflammatory HGF/c-Met system might contribute to the atheroprotective mechanisms of MLT.

Outcome, Return to Work and Health-Related Costs After Aneurysmal Subarachnoid Hemorrhage.

OBJECT: Data on health-related costs after aneurysmal subarachnoid hemorrhage (aSAH) are limited. The aim was to evaluate outcome, return to work and costs after aSAH with focus on differences between high- and low-grade aSAH (defined as World Federation of Neurological Surgeons [WFNS] grades 4-5 and WFNS 1-3, respectively). METHODS: A cross-sectional study was performed, including all consecutive survivors of aSAH over a 4-year period. A telephone interview was conducted to assess the Glasgow Outcome Scale Extended and employment status before and after aSAH. Direct costs were calculated by multiplying the length of hospitalization by the average daily costs. Indirect costs were calculated for productivity losses until retirement age according to the human capital approach. RESULTS: Follow-up was performed 2.7 years after aSAH (range 1.3-4.6). Favorable outcome was achieved in 114 of 150 patients (76%) and work recovery in 61 of 98 patients (62%) employed prior to aSAH. High-grade compared to low-grade aSAH resulted less frequently in favorable outcome (52% vs. 85%; p < 0.001) and work recovery (39% vs. 69%; p = 0.013). The total costs were € 344.277 (95% CI 268.383-420.171) per patient, mainly accounted to indirect costs (84%). The total costs increased with increasing degree of disability and were greater for high-grade compared to low-grade aSAH (€ 422.496 vs. € 329.193; p = 0.039). The effective costs per patient with favorable outcome were 2.1-fold greater for high-grade compared to low-grade aSAH (€ 308.625 vs. € 134.700). CONCLUSION: Favorable outcome can be achieved in a considerable proportion of high-grade aSAH patients, but costs are greater compared to low-grade aSAH. Further cost-effectiveness studies in the current era of aSAH management are needed.

Non-invasive imaging techniques and assessment of carotid vasa vasorum neovascularization: Promises and pitfalls.

Carotid adventitia vasa vasorum neovascularization (VVn) is associated with the initial stages of arteriosclerosis and with the formation of unstable plaque. However, techniques to accurately quantify that neovascularization in a standard, fast, non-invasive, and efficient way are still lacking. The development of such techniques holds the promise of enabling wide, inexpensive, and safe screening programs that could stratify patients and help in personalized preventive cardiovascular medicine. In this paper, we review the recent scientific literature pertaining to imaging techniques that could set the stage for the development of standard methods for quantitative assessment of atherosclerotic plaque and carotid VVn. We present and discuss the alternative imaging techniques being used in clinical practice and we review the computational developments that are contributing to speed up image analysis and interpretation. We conclude that one of the greatest upcoming challenges will be the use of machine learning techniques to develop automated methods that assist in the interpretation of images to stratify patients according to their risk.

Sensitivity of Computed Tomography for the Assessment of Spontaneous Dermoid Cyst Localized Rupture with Granulomatous Reaction.

PURPOSE: To assess the sensitivity of computed tomography for the diagnosis of spontaneous localized orbital dermoid cyst rupture with granulomatous reaction. METHODS: The charts of 42 patients with dermoid cysts were reviewed retrospectively. The data collected included demographics, clinical features, CT imaging, and postoperative histopathological analysis of the lesions. The association between radiological signs of inflammation and histopathological evidence of an inflammatory reaction was tested by univariate logistic regression. RESULTS: Localized spontaneous rupture with granulomatous reaction occurred in 61.9% of patients. The median age of patients with spontaneous rupture was significantly higher than the age of patients who had no histopathological evidence of rupture. Bone scalloping was significantly associated with preoperative rupture. Fat contents had a protective effect. Large sizes increased the odds of rupture. CONCLUSION: Bone remodeling and histopathological evidence of spontaneous preoperative rupture were significantly associated. Since age, cyst size, and contents are factors contributing to rupture, surgical removal is suggested for dermoids with liquid contents.

Readmission After Aneurysmal Subarachnoid Hemorrhage: A Nationwide Readmission Database Analysis.

BACKGROUND AND PURPOSE: The goal of this nationwide study is to evaluate the suitability of readmission as a quality indicator in the aneurysmal subarachnoid hemorrhage (SAH) population. METHODS: Patients with aneurysmal SAH were extracted from the Nationwide Readmission Database (2013). Multivariable Cox proportional hazard regression was used to evaluate predictors of a 30-day readmission, and multivariable linear regression was used to analyze the association of hospital readmission rates with hospital mortality rates. Predictors screened included patient demographics, comorbidities, severity of SAH, complications from the SAH hospitalization, and hospital characteristics. RESULTS: The 30-day readmission rate was 10.2% (n=346) among the 3387 patients evaluated, and the most common reasons for readmission were neurological, hydrocephalus, infectious, and venous thromboembolic complications. Greater number of comorbidities, increased severity of SAH, and discharge disposition other than to home were independent predictors of readmission (P≤0.03). Although hydrocephalus during the SAH hospitalization was associated with readmission for the same diagnosis, other readmissions were not associated with having sustained the same complication during the SAH hospitalization. Hospital mortality rate was inversely associated with hospital SAH volume (P=0.03) but not significantly associated with hospital readmission rate; hospital SAH volume was also not associated with SAH readmissions. CONCLUSIONS: In this national analysis, readmission was primarily attributable to new medical complications in patients with greater comorbidities and severity of SAH rather than exacerbation of complications from the SAH hospitalization. Additionally, hospital readmission rates did not correlate with other established quality metrics. Therefore, readmission may be a suboptimal quality indicator in the SAH population.

Chordae Tendineae Rupture in the United States: Trends of Outcomes, Costs and Surgical Interventions.

OBJECTIVES: To describe national trends in the incidence and outcomes of patients with chordae tendineae rupture (CTR). METHODS: Patients who were diagnosed with CTR between 2000 and 2012 were identified in National (Nationwide) Inpatient Sample (NIS) registry. CTR was defined using validated International Classification of Diseases, 9th Edition, Clinical Modification diagnosis (ICD9-CM) codes. Results: A total of 37,287 (14,833 mitral valve repair, 7780 mitral valve replacement) CTR cases were identified. Overall, in-hospital mortality in CTR decreased by 3% from 2000 to 2012 (P < 0.001). From 2000 to 2012, the rate of mitral valve repair increased from 27.2% to 46.4%, (P < 0.001) with a concurrent decrease in the rate of mitral valve replacement (from 27.8 to 17.7%, P < 0.001). After multivariate adjustment, patient age (OR = 1.04, 95% CI 1.03-1.06, P < 0.001), congestive heart failure (CHF) (OR = 2.08, 95% CI 1.19-3.64, P = 0.01), myocardial infarction (MI) (OR = 3.58, 95% CI 2.10-6.11, P < 0.001), Deyo/Charlson comorbidity index (OR = 1.23, 95% CI 1.07-1.41, P < 0.003) and use of the intra aortic balloon pump (IABP) (OR = 4.81 95% CI 2.71-8.55, P < 0.001) were found to be independently associated with greater odds of mortality in these patients. Additionally, mitral valve replacement was significantly associated with higher costs of hospitalization (coefficient 15693, 95% CI 12638-18749, P < 0.001)Conclusion: Mitral valve repair is associated with reduced inpatient mortality and costs compared with mitral valve replacement. A substantial increase in the percentage of cases undergoing mitral valve repair with a concurrent decrease in cases undergoing mitral valve replacement were observed. Increasing age and comorbidity index, history of CHF and MI, and use of IABP were identified as factors that could increase the risk of mortality in patients with CTR.

Assessment of the vulnerable carotid atherosclerotic plaque using contrast-enhanced ultrasonography.

Carotid atherosclerosis represents a primary cause for cerebrovascular ischemic events and its contemporary management includes surgical revascularization for moderate to severe symptomatic stenoses. However, the role of invasive therapy seems to be questioned lately for asymptomatic cases. Numerous reports have suggested that the presence of neovessels within the atherosclerotic plaque remains a significant vulnerability factor and over the last decade imaging modalities have been used to identify intraplaque neovascularization in an attempt to risk-stratify patients and offer management guidance. Contrast-enhanced ultrasonography of the carotid artery is a relatively novel diagnostic tool that exploits resonated ultrasound waves from circulating microbubbles. This property permits vascular visualization by producing superior angiography-like images, and allows the identification of vasa vasorum and intraplaque microvessels. Moreover, plaque neovascularization has been associated with plaque vulnerability and ischemic symptoms lately as well. At the same time, attempts have been made to quantify contrast-enhanced ultrasonography signal using sophisticated software packages and algorithms, and to correlate it with intraplaque microvascular density. The aim of this review was to collect all recent data on the characteristics, performance, and prognostic role of contrast-enhanced ultrasonography regarding carotid stenosis management, and to produce useful conclusions for clinical practice.

Sex Differences in Nonculprit Coronary Plaque Microstructures on Frequency-Domain Optical Coherence Tomography in Acute Coronary Syndromes and Stable Coronary Artery Disease.

BACKGROUND: Numerous reports suggest sex-related differences in atherosclerosis. Frequency-domain optical coherence tomography has enabled visualization of plaque microstructures associated with disease instability. The prevalence of plaque microstructures between sexes has not been characterized. We investigated sex differences in plaque features in patients with coronary artery disease. METHODS AND RESULTS: Nonculprit plaques on frequency-domain optical coherence tomography imaging were compared between men and women with either stable coronary artery disease (n=320) or acute coronary syndromes (n=115). A greater prevalence of cardiovascular risk factors was observed in women. Nonculprit plaques in women with stable coronary artery disease were more likely to exhibit plaque erosion (8.6% versus 0.3%; P=0.03) and a smaller lipid arc (163.1±71.4° versus 211.2±71.2°; P=0.03), and less likely to harbor cholesterol crystals (17.2% versus 27.5%; P=0.01) and calcification (15.4% versus 34.4%; P=0.008), whereas fibrous cap thickness (105.2±62.1 versus 96.1±40.4 µm; P=0.57), the prevalence of thin-cap fibroatheroma (26.5% versus 25.2%; P=0.85), and microchannels (19.2% versus 20.5%; P=0.95) were comparable. In women with acute coronary syndrome, a smaller lipid arc (171.6±53.2° versus 235.8±86.4°; P=0.03), a higher frequency of plaque erosion (11.4% versus 0.6%; P=0.04), and a lower prevalence of cholesterol crystal (28.6% versus 38.2%; P=0.03) and calcification (10.0% versus 23.7%; P=0.01) were observed. These differences persisted after adjusting clinical demographics. Although thin-cap fibroatheromas in men clustered within proximal arterial segments, thin-cap fibroatheromas were evenly distributed in women. CONCLUSIONS: Despite more comorbid risk factors in women, their nonculprit plaques exhibited more plaque erosion, and less cholesterol and calcium content. This distinct phenotype suggests sex-related differences in the pathophysiology of atherosclerosis.

Prospective Assessment of a Symptomatic Cerebral Vasospasm Predictive Neural Network Model.

INTRODUCTION: The author introduced a symptomatic cerebral vasospasm (SCV) prediction model built with freeware based on a 91-patient dataset. In a prospective test group of 22 patients at the same hospital, this model outperformed logistic regression models in vasospasm prediction on the basis of the same datasets. One of the model's limitations was a question of reproducibility in other centers. In this report, the author describes his experience with the prospective use of the model at a different hospital with a different population setting. METHODS: Patient data of 25 consecutive cases of aneurysm rupture were prospectively assessed by the model to predict SCV. The prediction was then compared with actual outcome. For the purpose of this report, SCV is defined as a delayed focal decline in neurological examination correlated with an area of radiographic vasospasm. This serves as the primary end point of the predictive model. Each case prediction is reported, along with strength of prediction, which is built into the model. The model's positive predictive value, negative predictive value, and sensitivity and specificity are reported. RESULTS: Twenty-five patients are included in the analysis. Six patients (24%) were diagnosed with SCV. The model predicted 9 patients would have SCV (positive predictive value 67%). The model predicted 16 patients would not have SCV (negative predictive value 100%). The sensitivity of the model was 100%, and the specificity of the model was 84%. DISCUSSION: The present analysis displays the predictive value of a neural network to model symptomatic cerebral vasospasm.

A Sanitary Pad for Self-Assessment of Rupture of Membranes.

BACKGROUND: Multistep immunoassay kits for the diagnosis of rupture of membranes are relatively complex and are not designed to be used by pregnant women themselves. These kits require procedural steps of specimen extraction and preparation. We evaluated the ability of a sanitary pad containing a qualitative immunoassay for alpha-fetoprotein (AFP) to serve as a one-step self-test to detect amniotic fluid leakage. TECHNIQUE: Four sets of pads were evaluated. The pads in the study set were worn by 288 pregnant women with confirmed rupture of membranes. Three controls were evaluated: 1) pads worn by 93 pregnant women with intact membranes, 2) additional pads instilled with urine specimens obtained from the 381 women described previously (study set plus control set 1), and 3) pads instilled with semen collected from 40 men. EXPERIENCE: All 288 pads that absorbed amniotic fluid had positive results. Approximately half of the pads absorbed with normal vaginal discharge had a sufficient amount to yield valid results, which were all negative. All 381 pads with instilled urine and all 40 pads with instilled semen had negative results. CONCLUSION: An immunoassay for AFP, embedded in a pad, appears to be a feasible and reproducible self-test for the detection of rupture of membranes.

The costs of elective and emergency abdominal aortic aneurysm repair: a comparative single centre study.

AIM: Population-based screening for abdominal aortic aneurysms (AAA) is being considered in New Zealand. However, there is a lack of data to support its cost effectiveness in this country. The aim of this study was to compare the hospital costs of AAA repair in emergency and elective cases over a 3-year period in a single centre in New Zealand. METHODS: A retrospective observational analysis of consecutive patients undergoing elective and emergency AAA repair during the study period (January 2009 to December 2011) was performed. RESULTS: A total of 169 AAA repairs were performed during the study period, of which 114 (67%) were open repairs. Sixty-four of these were open elective AAA repairs, 40 were open ruptured repairs, and 10 were open symptomatic repairs. The mean inpatient cost was $38,804 for open ruptured AAA repair and $28,019 for open elective repair, a difference of $10,785 (95%CI: $249 to $21,321; p=.045). The costs of blood products and laboratory investigations were significantly greater in the ruptured group than the elective. There was no significant difference in length of hospital admission between the groups. CONCLUSIONS: This study demonstrates that ruptured AAA repairs are more expensive than elective AAA repairs, despite no difference in length of hospital stay. The estimated inpatient costs documented in this study for each type of repair can be used for cost-effectiveness analysis in New Zealand. A screening program that reduces the incidence of surgery for ruptured AAA could decrease the average inpatient cost of AAA repairs.

Incremental prognostic value of quantitative plaque assessment in coronary CT angiography during 5 years of follow up.

OBJECTIVE: We sought to assess the incremental prognostic value of quantitative plaque characterization beyond established CT risk scores. BACKGROUND: Several plaque characteristics detectable by coronary computed tomographic angiography (coronary CTA) are thought to be indicative of vulnerable plaques and subsequent cardiac events, particularly low attenuation plaque volume (LAPV), positive remodeling and the napkin-ring sign which is high density vascular adhesion with a small center of low density. It is unknown how quantitative plaque assessment can contribute to the long-term prediction of cardiovascular events in relation to established CT risk scores such as the calcium score or Segment Stenosis Score (SSS). METHODS: In 1168 consecutive patients with suspected coronary artery disease (CAD), calcium score measurement and coronary plaque characterization was performed comprising the presence of calcified, non-calcified, and partially calcified plaques on a per-segment basis. In all non-calcified or partially calcified plaques, semi-automated plaque analysis was performed to quantify low attenuation plaque volume (density <30 HU), total non-calcified plaque volume (<150 HU, TNCPV) and remodeling index. The presence of the napkin-ring sign was assessed visually. The study endpoint was the occurrence of major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction and coronary revascularization more than 90 days after coronary CTA. RESULTS: During a clinical follow up of 5.7 years, MACE was observed in 46 patients (3.9%). All plaque characteristics were associated with MACE. The strongest association was observed for LAPV (HR 1.12, p < 0.0001). LAPV showed incremental prognostic value in a stepwise multivariable model including the Morise Score for clinical risk, calcium score and SSS (p = 0.036). CONCLUSION: LAPV, TPV, PR and presence of the napkin-ring sign are predictors of MACE independently of clinical risk presentation. LAPV carries slight additional prognostic information beyond the calcium score and conventional coronary CTA analysis. It may therefore improve risk prediction after CT imaging.

Gender differences in plaque characteristics of culprit lesions in patients with ST elevation myocardial infarction.

There is limited research on plaque characteristics of ST elevation myocardial infarction (STEMI) patients according to the gender and age. 280 Consecutive STEMI patients who underwent VH-IVUS imaging on culprit before percutaneous coronary intervention (PCI) were enrolled in this study. Women were significantly older than men (69.8 ± 10 vs. 55.9 ± 11.3, p < 0.001). After propensity matching, men had higher plaque burden (79.7 ± 7.8 vs. 73.7 ± 13.0 %, p = 0.010), more fibro-fatty tissue (12.8 ± 9.9 vs. 9.5 ± 6.8 %, p = 0.04) and less dense calcium than women (8.4 ± 5.8 vs. 12.3 ± 8.7 %, p = 0.007). Subgroups dividing by 50, 65, 75 years old, plaque burden was higher in elderly men aged 66-75 years compared to the young men aged less than 50 (75.5 ± 9.2 vs. 68.4 ± 10.1 %, p = 0.012). And middle aged men ranged 51-65 years showed significantly more plaque burden at minimal lumen area site than matched aged women (77.5 ± 8.0 vs. 69.0 ± 17.6 %, p = 0.012). Elderly women aged 66-75 years showed significantly more necrotic core (28.6 ± 7.3 %) and dense calcium (14.9 ± 7.5 %) compared to all the younger or matched subgroups of men. These differences in plaque composition are blunted in the very elderly of men and women aged over 75 years. The findings may explain the gender differences in clinical prognosis in STEMI patients.

Plaque assessment by coronary CT.

Coronary CT angiography (CTA) has emerged as a highly reliable and non-invasive modality for the exclusion of coronary artery disease. Recent technological advancements in coronary CTA imaging allow for robust qualitative and quantitative assessment of atherosclerotic plaques. Furthermore, CTA is a promising modality for functional evaluation of coronary lesions. Individual plaque features, the extent and severity of atherosclerotic plaque burden were proposed to improve cardiovascular risk stratification. It has been suggested that total atherosclerotic plaque burden is a stronger predictor of coronary events than total ischemia burden. The quest to noninvasively detect individual vulnerable plaques still remains. In the current review we sought to summarize state-of-the-art coronary artery plaque assessment by CTA.