Overall survival comparison between pediatric and adult Ewing sarcoma of bone and adult nomogram construction: a large population-based analysis.

Background: Ewing sarcoma (ES) is a common primary bone tumor in children. Our study aimed to compare overall survival (OS) between pediatric and adult bone ES patients, identify independent prognostic factors and develop a nomogram for predicting OS in adult patients with ES of bone. Methods: We retrospectively analyzed data for the 2004-2015 period from the Surveillance, Epidemiology, and End Results (SEER) database. To guarantee well-balanced characteristics between the comparison groups, propensity score matching (PSM) was used. Kaplan-Meier (KM) curves were used to compare OS between pediatric and adult patients with ES of bone. Univariate and multivariate Cox regression analyses were used to screen independent prognostic factors for ES of bone, and a prognostic nomogram was constructed by using the factors identified. The prediction accuracy and clinical benefit were evaluated using receiver operating characteristic (ROC) curves, areas under the curves (AUCs), calibration curves, and decision curve analysis (DCA). Results: Our results showed that adult ES patients had lower OS than younger ES patients. Age, surgery, chemotherapy, and TNM stage were independent risk factors for bone ES in adults and were used to develop a nomogram. AUCs for 3-, 5-, and 10-year OS were 76.4 (67.5, 85.3), 77.3 (68.6, 85.9) and 76.6 (68.6, 84.5), respectively. Calibration curves and DCA results indicated excellent performance for our nomogram. Conclusion: We found that ES pediatric patients have better OS than adult ES patients, and we constructed a practical nomogram to predict the 3-, 5- and 10-year OS of adult patients with ES of bone based on independent prognostic factors (age, surgery, chemotherapy, T stage, N stage and M stage).

Management of Severe Coarctation of the Aorta and Bilateral Carotid Artery Stenosis: An Interventional Catch-22.

We present a case of an adult with concurrent severe aortic coarctation, bilateral carotid artery stenosis, and anomalous right subclavian artery, posing the interventional dilemma of accepting potential cerebral hyperperfusion syndrome vs hypoperfusion ischemic injury. Transcatheter stenting of the aortic coarctation was successfully performed without any neurological deficits. (Level of Difficulty: Beginner.).

Socioeconomic status influences on bone mineral density in American men: findings from NHANES 2011-2020.

The association between socioeconomic status (SES) and bone mineral density (BMD) in men remains controversial. We showed that SES was positively associated with BMD in American men. Confounding factors like race/ethnicity and age could affect the association. INTRODUCTION: Based on the data from the National Health and Nutrition Examination Survey (NHANES), 2011-2020, this article aims to investigate the association of SES (poverty income ratio (PIR) and education level) with the BMD in American men. METHODS: We evaluated the association of SES with BMD in 4446 men aged ≥ 20 years (mean age, 41.0 ± 13.4 years) from the NHANES 2011-2020. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine. We used multivariate linear regression models to examine the relationship between SES and total spine BMD, adjusted for a large range of confounding factors. RESULTS: Compared with other PIR quarters, individuals in the highest quarter of PIR were more likely to be older and white and had fewer smoking or drinking behaviors. After adjusting for race/ethnicity, age, drinking and smoking behavior, body mass index (BMI), total protein, serum calcium, serum uric acid, cholesterol, serum phosphorus, and blood urea nitrogen, PIR was positively correlated with total spine BMD (ß = 0.004 95% CI: 0.001-0.007, P = 0.006). Individuals with the highest degree (college degree or above) had a 0.057 g/cm2 greater BMD than that of the lowest degree (less than 9th grade) (ß = 0.057 95% CI: 0.037-0.077, P < 0.001). CONCLUSIONS: Our study indicates that SES was positively associated with the lumbar BMD among American men. Clinicians, healthcare providers, and policymakers should consider the unequal SES of men when implementing osteoporosis prevention and treatment strategies.

Predicting Patients With Troponin Positive Chest Pain and Unobstructed Coronary Arteries With Electrocardiogram, Troponin Kinetics and GRACE Score.

BACKGROUND: Troponin positive chest-pain with unobstructed coronary arteries (TPCP-UCA), occurs in 6% of cases of patients presenting with acute coronary syndrome (ACS). Whilst TPCP-UCA patients are known to be younger with less cardiovascular risk factors when compared to obstructive coronary disease (MICAD), no validated methods exist to reliably delineate these two conditions prior to coronary angiography. METHODS: We analysed 142 patients with MICAD and 127 patients with TPCP-UCA from 2015 to 2019. Several key predetermined clinical, biochemical and electrocardiograph (ECG) parameters, as well as Global Registry of Acute Coronary Events (GRACE) score, were collected for all patients. All TPCP-UCA patients underwent cardiac magnetic resonance imaging (cMRI). RESULTS: Patients with TPCP-UCA were younger than MICAD (44 vs 68 yrs, p<0.01), and with less cardiac risk factors of hypertension (31% vs 68%, p<0.01), hypercholesterolaemia (23% vs 56%, p<0.01), diabetes (11% vs 45%, p<0.01), prior ischaemic heart disease (8% vs 42%, p<0.01) and smoking history (29% vs 50%, p<0.01). Peak troponin (MICAD 2,084.5 ng/L vs TPCP-UCA 847.0 ng/L, p=0.02), serial-to-initial troponin ratio (MICAD 13.5 vs TPCP-UCA 5.1, p<0.01), and peak-to-initial troponin ratio (MICAD 69.6 vs TPCP-UCA 14.0, p<0.01) were all higher in the MICAD group. GRACE scores were significantly different across the two cohorts (TPCP UCA 74 vs MICAD 106, p<0.01), with a receiver operator characteristic (ROC) curve statistic of 0.794 (95% CI 0.739-0.850). On ECG analysis, MICAD had greater prevalence and sum of ST depression (40% vs 19% p<0.01; 1.6 mm vs 0.44 mm, p<0.01) and T wave inversion (37% vs 17%, p<0.01), whilst TPCP-UCA had greater presence of PR depression (20% vs 3% p<0.01), and longer repolarisation (T wave peak to end 89 ms vs 83 ms, p=0.04; T wave peak to end/corrected QT 0.208 ms vs 0.193 ms, p=0.03). All TPCP-UCA patients underwent cMRI. Aetiology was found in 82% of cases, with the leading diagnosis being myocarditis (58%), followed by infarction (8%), whilst 18% had a normal cMRI. CONCLUSIONS: TPCP-UCA is an important differential for patients presenting with ACS, and has several key demographic, biochemical and electrocardiographic differences. The present findings are hypothesis generating, thus prospective studies are required to determine and validate potential clinical utility.

Prevalence and treatment rate of osteoporosis in patients undergoing total knee and hip arthroplasty: a systematic review and meta-analysis.

PURPOSE: Due to age and gender, patients awaiting total knee or hip arthroplasty (TKA/THA) are at a higher risk of osteoporosis. In joint arthroplasty, low bone mineral density (BMD) is a risk factor for implant osseointegration, durability, and prosthesis complications. This study aims to investigate the prevalence and treatment rate of osteoporosis in patients undergoing total joint arthroplasty (TJA). METHODS: We applied a comprehensive literature search through PubMed, Cochrane Library, and EMBASE from inception to July 10, 2021, for studies investigating the prevalence and treatment rate of osteoporosis in TJA patients. The aggregated prevalence was calculated with the random-effects model, and the heterogeneity between studies was checked by Cochran's Q test and quantified by the I2 statistic. We performed subgroup analyses and meta-regression analyses to determine the source of heterogeneity. Publication bias was assessed by a funnel plot and verified by Egger's test. Anti-osteoporosis treatment for TJA patients was described qualitatively and quantitatively. RESULTS: Of 4561 citations identified by the search strategy, 11 studies including 3462 patients were eligible for inclusion. The pooled prevalence of osteoporosis and osteopenia in TJA patients was 24.8% (95%CI: 14.1-37.2%) and 38.5% (95%CI: 29.3-48.0%), respectively. The prevalence of osteoporosis/osteopenia in TJA patients was 64.0% (95%CI: 45.8-80.3%). In terms of gender, the pooled prevalence of osteoporosis in males, females, and postmenopausal females were 5.5% (95%CI: 1.5-11.4%), 29.0% (95%CI: 18.3-41.1%), and 38.3% (95%CI: 13.2-67.1%), respectively. The treatment rate of osteoporosis in TJA patients was 32.9% (95%CI: 15.2-53.1%) by a random-effects model. CONCLUSIONS: Osteoporosis is highly prevalent in patients undergoing TJA, especially in postmenopausal females. However, the treatment rate of osteoporosis is low. Considering the possibility of surgical complications, clinicians should strengthen their awareness of pre-operative BMD assessment and manage osteoporosis in high-risk patients.

Androgens Stimulate EPC-Mediated Neovascularization and Are Associated with Increased Coronary Collateralization.

Endothelial progenitor cells (EPCs) play a key role in neovascularization and have been linked to improved cardiovascular outcomes. Although there is a well-established inverse relationship between androgen levels and cardiovascular mortality in men, the role of androgens in EPC function is not fully understood. In this study, we investigated the effects of androgens on 2 subpopulations of EPCs, early EPCs (EEPCs) and late outgrowth EPCs (OECs), and their relationships with coronary collateralization. Early EPCs and OECs were isolated from the peripheral blood of young healthy men and treated with dihydrotestosterone (DHT) with or without androgen receptor (AR) antagonist, hydroxyflutamide, in vitro. Dihydrotestosterone treatment enhanced AR-mediated proliferation, migration, and tubulogenesis of EEPCs and OECs in a dose-dependent manner. Furthermore, DHT augmented EPC sensitivity to extracellular stimulation by vascular endothelial growth factor (VEGF) via increased surface VEGF receptor expression and AKT activation. In vivo, xenotransplantation of DHT pretreated human EPCs augmented blood flow recovery and angiogenesis in BALB/c nude male mice, compared to mice receiving untreated EPCs, following hindlimb ischemia. In particular, DHT pretreated human OECs exhibited higher reparative potential than EEPCs in augmenting postischemic blood flow recovery in mice. Furthermore, whole blood was collected from the coronary sinus of men with single vessel coronary artery disease (CAD) who underwent elective percutaneous intervention (n = 23). Coronary collateralization was assessed using the collateral flow index. Serum testosterone and EPC levels were measured. In men with CAD, circulating testosterone was positively associated with the extent of coronary collateralization and the levels of OECs. In conclusion, androgens enhance EPC function and promote neovascularization after ischemia in mice and are associated with coronary collateralization in men.

Arrhythmogenic Cardiomyopathy in 2018-2019: ARVC/ALVC or Both?

Arrhythmogenic cardiomyopathy (ACM) is now commonly used to describe any form of non-hypertrophic, progressive cardiomyopathy characterised by fibrofatty infiltration of the ventricular myocardium. Right ventricular (RV) involvement refers to the classical arrhythmogenic right ventricular cardiomyopathy, but left ventricular, or bi-ventricular involvement are now recognised. ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. ACM classically manifests as ventricular arrhythmias, and sudden death may be the first presentation of the disease. Heart failure is seen with advanced stages of the disease. Diagnosis can be challenging due to variable expressivity and incomplete penetrance, and is guided by established Taskforce criteria that incorporate electrical features (12-lead electrocardiography (ECG), features of ventricular arrhythmias), structural features (on imaging via echo and cardiac magnetic resonance imaging [MRI]), tissue characteristics (via biopsy), and familial/genetic evaluation. Electrical abnormalities may precede structural alterations, which also make diagnosis challenging, especially in differentiating ACM from other conditions such as benign right ventricular arrhythmias, channelopathies such as Brugada, or the Athlete's Heart. Genetic testing is critical in identifying familial mutations and initiating cascade testing, but finds a pathogenic mutation in only ∼50% of patients. Some critical genotype-phenotype correlations do exist and may help guide risk stratification and give clues to disease progression. Therapeutic strategies include restriction from high endurance and competitive sports, ß-blockers, antiarrhythmic drugs, heart failure medications, implantable cardioverter-defibrillators and combined endocardial/epicardial catheter ablation. Ablation has emerged as the treatment of choice for recurrent ventricular arrhythmias in ACM. This state-of-the-art review outlines the pathogenesis, diagnosis and treatment of ACM in the contemporary era.

Myocardial Viability: From Proof of Concept to Clinical Practice.

Ischaemic left ventricular (LV) dysfunction can arise from myocardial stunning, hibernation, or necrosis. Imaging modalities have become front-line methods in the assessment of viable myocardial tissue, with the aim to stratify patients into optimal treatment pathways. Initial studies, although favorable, lacked sufficient power and sample size to provide conclusive outcomes of viability assessment. Recent trials, including the STICH and HEART studies, have failed to confer prognostic benefits of revascularisation therapy over standard medical management in ischaemic cardiomyopathy. In lieu of these recent findings, assessment of myocardial viability therefore should not be the sole factor for therapy choice. Optimization of medical therapy is paramount, and physicians should feel comfortable in deferring coronary revascularisation in patients with coronary artery disease with reduced LV systolic function. Newer trials are currently underway and will hopefully provide a more complete understanding of the pathos and management of ischaemic cardiomyopathy.

Cardiac Magnetic Resonance Imaging Predictors of Short-Term Outcomes after High Risk Coronary Surgery.

BACKGROUND: The euroSCORE II is a widely used pre-coronary artery bypass graft surgery (CAGS) risk score, but its predictive power lacks the specificity to predict outcomes in high-risk patients (16) and left ventricular (LV) dysfunction (<40%) based on 2D-echocardiography who underwent CAGS and in whom CMRI (1.5T) was performed preoperatively were retrospectively studied. Cardiac magnetic resonance imaging parameters were assessed in patients who either had complications immediately post-surgery (n=35), six weeks post-surgery (n=20) or were uncomplicated. RESULTS: The average age of patients recruited was 69±5 years with high euroSCORE II (22±4) and low 2D-echocardiography LV ejection fraction (38%±2%). Cardiac magnetic resonance imaging results demonstrated that those with immediate complications had higher LV scar/infarct burden as a proportion of LV mass (17±3% vs 10±3%; p=0.04) with lower circumferential relaxation index (2.5±0.46 vs 2.8±0.56; p=0.05) compared to those with no complications. Early mortality from surgery was 17% (n=9) and was associated with lower RV stroke volume (55±12 vs 68±18; p=0.03) and higher LV infarct scar/burden (18±2% vs 10±2%, p=0.04). Cardiac magnetic resonance imaging showed patients with complications at six weeks post-surgery had higher LV scar/infarct burden (14.5±2% vs 6.8±2%, p=0.03) compared to those without complications. CONCLUSION: Cardiac magnetic resonance imaging preoperative LV and RV parameters are valuable in assessing the likelihood of successful outcomes from CAGS in high-risk patients with LV dysfunction.

An Intelligent Model for Pairs Trading Using Genetic Algorithms.

Pairs trading is an important and challenging research area in computational finance, in which pairs of stocks are bought and sold in pair combinations for arbitrage opportunities. Traditional methods that solve this set of problems mostly rely on statistical methods such as regression. In contrast to the statistical approaches, recent advances in computational intelligence (CI) are leading to promising opportunities for solving problems in the financial applications more effectively. In this paper, we present a novel methodology for pairs trading using genetic algorithms (GA). Our results showed that the GA-based models are able to significantly outperform the benchmark and our proposed method is capable of generating robust models to tackle the dynamic characteristics in the financial application studied. Based upon the promising results obtained, we expect this GA-based method to advance the research in computational intelligence for finance and provide an effective solution to pairs trading for investment in practice.

The relationship between endothelial progenitor cell populations and epicardial and microvascular coronary disease-a cellular, angiographic and physiologic study.

BACKGROUND: Endothelial progenitor cells (EPCs) are implicated in protection against vascular disease. However, studies using angiography alone have reported conflicting results when relating EPCs to epicardial coronary artery disease (CAD) severity. Moreover, the relationship between different EPC types and the coronary microcirculation is unknown. We therefore investigated the relationship between EPC populations and coronary epicardial and microvascular disease. METHODS: Thirty-three patients with a spectrum of isolated left anterior descending artery disease were studied. The coronary epicardial and microcirculation were physiologically interrogated by measurement of fractional flow reserve (FFR), index of microvascular resistance (IMR) and coronary flow reserve (CFR). Two distinct EPC populations (early EPC and late outgrowth endothelial cells [OECs]) were isolated from these patients and studied ex vivo. RESULTS: There was a significant inverse relationship between circulating OEC levels and epicardial CAD severity, as assessed by FFR and angiography (r=0.371, p=0.04; r=-0.358, p=0.04; respectively). More severe epicardial CAD was associated with impaired OEC migration and tubulogenesis (r=0.59, p=0.005; r=0.589, p=0.004; respectively). Patients with significant epicardial CAD (FFR<0.75) had lower OEC levels and function compared to those without hemodynamically significant stenoses (p<0.05). In contrast, no such relationship was seen for early EPC number and function, nor was there a relationship between IMR and EPCs. There was a significant relationship between CFR and OEC function. CONCLUSIONS: EPC populations differ in regards to their associations with CAD severity. The number and function of OECs, but not early EPCs, correlated significantly with epicardial CAD severity. There was no relationship between EPCs and severity of coronary microvascular disease.

Impact of new task force criteria in the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that can lead to sudden cardiac death. The diagnostic criterion has recently been revised and through the use of cardiac magnetic resonance (CMR) imaging this study aimed to assess the clinical impact of comparing the original 1994 task force (TF) criterion to the revised 2010 criterion. METHODS: We evaluated 173 consecutive CMR scans of patients referred with clinical suspicion of ARVC between 2008 and 2011. We then compared the prevalence of major and minor CMR criteria by applying the two criteria. RESULTS: Using the 1994 TF criterion, 13 (7.5%) patients had definite, 11 (6.4%) had borderline, and 39 (22.5%) had possible ARVC. Using the 2010 TF criterion, 10 (5.8%) patients had definite, 1 had borderline, and 7 had (0.04%) possible ARVC. With the 1994 criterion, 81 patients satisfied CMR criterion, of which 36 (44%) had major and 45 (56%) had minor criteria. Upon reclassification with the revised criterion, 61 of the 81 patients were not assigned any criteria, even though many patients had significant risk factors. The negative predictive values (NPV) for both CMR criteria were 100% but the positive predictive values (PPV) for combined CMR major or minor criteria improved from 23% to 55%. CONCLUSIONS: Revision of the criterion has enhanced the diagnostic capabilities of CMR but has resulted in a large cohort of patients not classified. In these patients, there is presently no official consensus on imaging or clinical strategy for surveillance of the evolution of pathology over time.

Implantable devices and magnetic resonance imaging.

The indications for cardiovascular implantable electronic devices (CIEDs) are ever expanding, seemingly in parallel to the similar widespread increase in the use of magnetic resonance imaging (MRI), where there are clear advantages of imaging with no ionizing radiation and superior tissue contrast. However, CIEDs have traditionally been considered an absolute contraindication to MRI, posing a major limitation to investigating various pathologies after implantation of such devices. In the last decade the traditional paradigm of avoiding MRI in patients with CIEDs has been challenged with studies demonstrating relative safety at 1.5T under certain circumstances. Now with the recent approval of 'MR conditional' devices, it is becoming increasingly apparent that CIEDs should no longer be considered an absolute contraindication to MRI.