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Microsurgical denervation of the spermatic cord (MDSC) is a treatment option in patients with chronic orchialgia. This procedure requires precise care to avoid any thermal damage to crucial adjacent tissues (arteries, veins, and lymphatics). Monopolar electrocautery is the standard ligation energy source, but may cause extensive collateral damage to the tissues. However, CO2 laser is known to produce a very predictable tissue penetration and minimal collateral spread. The goal of this study was to compare the extent of collateral thermal damage in both monopolar electrocautery and CO2 laser ablation in the spermatic cord during a robotic assisted MDSC (RMDSC) procedure as well as the feasibility for utilizing the flexible fiber-optic CO2 laser probe after “RMDSC” procedure. RMDSC was performed using standard monopolar electrocautery on the spermatic cord of one side of a fresh human male cadaver (randomly selected) and then compared to RMDSC using the CO2 laser on the contralateral spermatic cord. Nine histological cross-sections from each cord were measured for depth of collateral thermal/cautery injury. The mean collateral thermal injury with CO2 laser was 0.17 ± 0.031 mm (range: 0.15–0.25 mm), and with standard electrocautery 0.72 ± 0.046 mm (range: 0.60–0.75 mm). CO2 laser resulted significantly less collateral thermal injury than standard electrocautery (p

Data on the prognostic value of regadenoson SPECT myocardial perfusion imaging (MPI) is limited and based on small cohorts. We conducted a single-center, retrospective cohort study of 10,275 consecutive patients who underwent regadenoson SPECT-MPI. Among the study subjects, 28.7% had abnormal MPI and 25.5% had myocardial ischemia. Patients were followed for a mean of 2.4 ± 2.2 years for major adverse cardiac events (MACE), defined as cardiac death or myocardial infarction. There was a significant stepwise increase in MACE with an increasing burden of perfusion abnormality (P

Background: Direct oral anticoagulants (DOACs) have been found to be similar or superior to warfarin in reducing ischemic stroke and intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF). We sought to examine the anticoagulation prescription patterns in community since the advent of DOACs and also evaluate the outcomes in terms of gastrointestinal (GI) bleeding, ischemic stroke, and ICH in real-world patients with AF receiving anticoagulation. Methods: This is a retrospective study comprising patients who were newly diagnosed with nonvalvular AF and were prescribed anticoagulants for stroke prevention. Prescription pattern of the anticoagulants based on CHA2DS2Vasc score was studied. Clinical outcomes of GI bleeding, ischemic stroke, and ICH were analyzed using a multivariate logistic regression model. Results: Of the 2362 patients with AF on anticoagulation, 44.7% were prescribed DOACs. Patients with CHA2DS2VASc score of ≥3 received a prescription for warfarin more often than DOACs ( P < .001). Multivariate logistic regression analysis revealed that the incidence of GI bleed (odds ratio [OR]: 0.91, 95% confidence interval [CI]: 0.62-1.35, P = .66) and stroke (OR: 0.77, 95% CI: 0.57-1.05, P = .10) was similar between warfarin and DOAC users. However, there was a trend toward lower ICH in the DOAC group (OR: 0.60, 95% CI: 0.36-1.01, P = .06). Conclusions: Prescription rate of DOACs for nonvalvular AF has increased significantly, with apixaban being the most commonly used agent. Patients with higher CHA2DS2-VASc score (≥3) are prescribed DOACs less often than warfarin. The reason for this discrepancy is unclear. Given the favorable risk–benefit profile of DOACs, further studies are needed to identify factors that determine anticoagulant selection in patients with AF with high thromboembolic risk.

To examine the utility and methods of coronary artery disease (CAD) assessment in patients with new-onset heart failure with reduced ejection fraction (HFrEF) of unclear etiology. Moreover, we sought to review the role and techniques of assessing myocardial viability to guide coronary revascularization in patients with established ischemic cardiomyopathy. Data indicates that surgical coronary revascularization in patients with HFrEF due to ischemic cardiomyopathy leads to lower long-term all-cause mortality and cardiovascular hospitalizations. Thus, identifying ischemic heart disease in patients with new-onset HFrEF is essential. In addition to invasive coronary angiography (ICA), radionuclide myocardial perfusion imaging, coronary CT angiography (CCTA), and cardiac magnetic resonance (CMR) imaging have emerged as effective non-invasive tools in the assessment of CAD in this population. Viability testing remains an area of particular interest and debate and its full potential has not been fully addressed. We propose stepwise algorithms for CAD and viability assessment in this patient population. Non-invasive testing with radionuclide myocardial perfusion imaging, CCTA, and CMR is an alternative to ICA for CAD assessment in patients with new-onset HFrEF of unclear etiology. Several non-invasive imaging modalities have proved to be effective in detecting viable myocardium in patients with ischemic cardiomyopathy. The use of viability imaging to guide coronary revascularization should be individualized.

Diabetes mellitus (DM), a modern-day epidemic, is a significant risk factor for cardiovascular disease. It is believed that statins elevate the risk of incident DM. Multiple trials were suggestive of the hyperglycemic effect of long-term statin use. This has prompted the Food and Drug Administration to include the risk of DM in the product label of statins. New-onset DM with statin use is biologically plausible and can be explained based on the multiple pathways in glucose metabolism affected by statins. Most pivotal clinical trials on statins were not powered to adequately assess the risk of incident DM with statin use, and the results from multiple meta-analyses are mixed. Currently, the US Preventive Services Task Force recommend the use of statins for primary prevention in patients with at least 1 cardiovascular risk factor and a 10-year risk of >7.5%. With the new American College of Cardiology/American Heart Association guidelines, the number of patients eligible for statin therapy has increased exponentially, which also calls for caution and increased vigilance in prescribing physicians regarding the controversies surrounding statin use. This article aims to highlight the existing data on statin use for primary prevention in diabetics and nondiabetics and the association of statins use with new-onset DM and its postulated mechanisms.

Atherosclerosis has long been known to be a chronic inflammatory disease. In addition, there is intense oxidative stress in atherosclerosis resulting from an imbalance between the excess reactive oxygen species (ROS) generation and inadequate anti-oxidant defense forces. The excess of the oxidative forces results in the conversion of low-density lipoproteins (LDL) to oxidized LDL (ox-LDL), which is highly atherogenic. The sub-endothelial deposition of ox-LDL, formation of foamy macrophages, vascular smooth muscle cell (VSMC) proliferation and migration, and deposition of collagen are central pathophysiologic steps in the formation of atherosclerotic plaque. Ox-LDL exerts its action through several different scavenger receptors, the most important of which is LOX-1 in atherogenesis. LOX-1 is a transmembrane glycoprotein that binds to and internalizes ox-LDL. This interaction results in variable downstream effects based on the cell type. In endothelial cells, there is an increased expression of cellular adhesion molecules, resulting in the increased attachment and migration of inflammatory cells to intima, followed by their differentiation into macrophages. There is also a worsening endothelial dysfunction due to the increased production of vasoconstrictors, increased ROS, and depletion of endothelial nitric oxide (NO). In the macrophages and VSMCs, ox-LDL causes further upregulation of the LOX-1 gene, modulation of calpains, macrophage migration, VSMC proliferation and foam cell formation. Soluble LOX-1 (sLOX-1), a fragment of the main LOX-1 molecule, is being investigated as a diagnostic marker because it has been shown to be present in increased quantities in patients with hypertension, diabetes, metabolic syndrome and coronary artery disease. LOX-1 gene deletion in mice and anti-LOX-1 therapy has been shown to decrease inflammation, oxidative stress and atherosclerosis. LOX-1 deletion also results in damage from ischemia, making LOX-1 a promising target of therapy for atherosclerosis and related disorders. In this article we focus on the different mechanisms for regulation, signaling and the various effects of LOX-1 in contributing to atherosclerosis.

Vitamin E is a lipid soluble vitamin comprising of eight natural isoforms, namely, α, β, δ, γ isoforms of tocopherol and α, β, δ, γ isoforms of tocotrienol. Many studies have been performed to elucidate its role in cancer. Until last decade, major focus was on alpha tocopherol and its anticancer effects. However, major clinical trials using alpha-tocopherol like SELECT trial and ATBC trial did not yield meaningful results. Hence there was a shift of focus to gamma-tocopherol, delta-tocopherol and tocotrienol. Unlike alpha-tocopherol, gamma-tocopherol and delta-tocopherol can scavenge reactive nitrogen species in addition to reactive oxygen species. Antiangiogenic effect, inhibition of HMG CoA reductase enzyme and inhibition of NF-κB pathway make the anti-cancer effects of tocotrienols unique compared to other vitamin E isoforms. Preclinical research on non-alpha tocopherol isoforms of vitamin E showed promising data on their anticancer effects. In this review, we deal with the current understanding on the potential mechanisms involved in the anticancer effects of vitamin E and the controversies in this field over last three decades. We also highlight the need to conduct further research on the anticancer effects of non-alpha-tocopherol isoforms in larger population and clinical setting.

OBJECTIVES Auscultation is an important clue to the presence of aortic stenosis (AS). We sought to assess the effect of symptom status, prior knowledge of diagnosis, and other patient factors on murmur detection. METHODS Patients with moderate-to-severe AS by echocardiography at a single center between June 2015 and June 2016 were included. Five consecutive patient encounters (inpatient and outpatient) within 12 months before the echocardiogram were analyzed. RESULTS Ninety-five patients (418 different clinician encounters) were studied. The murmur of AS was identified by only 39% of clinicians. In multivariate analysis, significant determinants of murmur detection were examination in outpatient setting (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.75-6.61), known history of AS (OR 2.77, 95% CI 1.53-5.01), female sex (OR 1.97, 95% CI 1.07-3.60), and presence of symptoms (OR 1.91 95% CI 1.12-3.26). Compared with the murmur detection findings by clinicians in medicine, the findings of surgical specialty clinicians were significantly lower (OR 0.12, 95% CI 0.06-0.26, P < 0.001). CONCLUSIONS In this real-world assessment, clinical context played an important role in the auscultation of AS murmur. The findings have important implications for the clinical diagnosis of asymptomatic advanced AS.

Oxidized LDL (ox-LDL) plays a central role in atherosclerosis by acting on multiple cells such as endothelial cells, macrophages, platelets, fibroblasts and smooth muscle cells through LOX-1. LOX-1 is a 50 kDa transmembrane glycoprotein that serves as receptor for ox-LDL, modified lipoproteins, activated platelets and advance glycation end-products. Ox- LDL through LOX-1, in endothelial cells, causes increase in leukocyte adhesion molecules, activates pathways of apoptosis, increases reactive oxygen species and cause endothelial dysfunction. In vascular smooth muscle cells and fibroblasts, they stimulate proliferation, migration and collagen synthesis. LOX-1 expressed on macrophages inhibit macrophage migration and stimulate foam cell formation. They also stimulate generation of metalloproteinases and contribute to plaque instability and thrombosis. Drugs that modulate LOX-1 are desirable targets against atherosclerosis. Many naturally occurring compounds have been shown to modulate LOX-1 expression and atherosclerosis. Currently, novel drug design techniques are used to identify molecules that can bind to LOX-1 and inhibit its activation by ox-LDL. In addition, techniques using RNA interference and monoclonal antibody against LOX-1 are currently being investigated for clinical use.

Background Heart failure (HF) is a major global health problem. Clinical trials test efficacy, effectiveness, and safety of novel and emerging therapies in HF. We sought to determine the salient features of ongoing interventional clinical trials in HF. Methods and Results We accessed the ClinicalTrials.gov registry of the National Institutes of Health (NIH) and the International Clinical Trials Registry Platform of the World Health Organization on January 1, 2017, and extracted pertinent information on current HF clinical trials for systematic review. Of 794 HF trials that met our inclusion criteria, almost one-half (49.1%) evaluated clinical end points and one-third (32.8%) examined imaging end points as primary outcomes. One-fourth (24.8%) were industry sponsored and one-third (35.6%) were university sponsored. The NIH and other United States federal agencies funded only 14 trials (1.8% of all trials; 10.7% of trials in the US). Among 536 HF trials with specified left ventricular ejection fraction status, 434 (81.0%) focused on HF with reduced ejection fraction (HFrEF) and only 102 (19.0%) trials targeted HF with preserved ejection fraction (HFpEF). Conclusions Ongoing HF trials are predominantly sponsored by nongovernmental funding agencies. Although HFpEF occurs as commonly as HFrEF in the community, the number of clinical trials targeting HFpEF is substantially lower compared with HFrEF.

Background: Electrocardiogram (ECG) differentiation of wide complex tachycardia (WCT) into ventricular tachycardia (VT) and supraventricular tachycardia with aberration (SVT-A) is often challenging. Objective: To determine if the presence of Q-waveforms (QS, Qr, QRs) in the inferior leads (II, III, aVF) can differentiate VT from SVT-A in a WCT compared to Brugada algorithm. We studied 2 inferior lead criteria namely QWC-A where all the inferior leads had a similar Q wave pattern and QWC-B where only lead aVF had a Q-waveform. Methods: A total of 181 consecutive cases of WCT were identified, digitally separated into precordial leads and inferior leads and independently reviewed by 2 electrophysiologists. An electrocardiographic diagnosis of VT or SVT-A was assigned based on Brugada and inferior lead algorithms. Results were compared to the final clinical diagnosis. Results: VT was the final clinical diagnosis in 24.9% of ECG cohort (45/181); 75.1% (136/181) were SVT-A. QWC-A and QWC-B had a high specificity (93.3% and 82.8%) and accuracy (78.2% and 71.0%), but low sensitivity (33.3% and 35.6%) in differentiating VT from SVT-A. The Brugada algorithm yielded a sensitivity of 82.2% and specificity of 68.4%. Area under the curve in ROC analysis was highest with Brugada algorithm (0.75, 95% CI 0.69-0.81) followed by QWC-A (0.63, 95% CI 0.56-0.70) and QWC-B (0.59, 95% CI 0.52-0.67). Conclusion: QWC-A and QWC-B criteria had poor sensitivity but high specificity in diagnosing VT in patients presenting with WCT. Further research combining this simple criterion with other newer diagnostic algorithms can potentially improve the accuracy of the overall diagnostic algorithm.

Oesophageal ultrasound with bronchoscope (EUS-B) is designed to evaluate mediastinal structures. We describe a case of a 78-year-old woman who presented with altered mental status for 2 weeks. CT head revealed a subacute infarct in the right middle cerebral artery distribution. She was also found to have a lung mass on chest imaging. EUS-B-guided fine needle aspiration demonstrated the presence of adenocarcinoma in station 7 lymph node and in the mass. Immunohistochemistry confirmed it to be a lung primary as the Thyroid Transcription Factor-1 (TTF-1) was strongly positive. During the procedure, the cardiac valves were evaluated, and a mitral valve vegetation was noted. Formal echocardiography confirmed the presence of the vegetation. During hospital stay, the patient developed fever. Her blood cultures grew oxacillin-resistant Staphylococcus aureus. She was subsequently treated for infective endocarditis. We suggest that the use of EUS-B to routinely scan adjacent structures during a procedure may help obtain additional clinical information that may be critical to patient management.