Dyslipidemia: The Role of Non-HDL Cholesterol, Apolipoprotein B, and Small, Dense LDL

Elevated low-density lipoprotein cholesterol (LDL-C) has traditionally been considered an independent risk factor for coronary artery disease (CAD). A level of LDL-C< 70 mg/dl is recommended for very high risk individuals. However, it has recently been suggested that the threshold for atherosclerosis may be much lower and it is widely accepted that even with the intense use of statins, not all cardiovascular adverse events are prevented. Consequently, new indexes have emerged that could outperform LDL-C especially in the highest risk populations, such as patients with diabetes type II or the metabolic syndrome. Non- high density lipoprotein (HDL) cholesterol is defined as all of the cholesterol that is not HDL (total cholesterol- HDL cholesterol). It has been shown that for each LDL-C category, an increase in non-HDL cholesterol increased the risk for cardiovascular disease. Prospective trials have also shown that total apo-B level reflects the total number of apo- B lipoproteins and measures the total atherogenic particle number. It seems that apo-B levels are much more closely related to the risk of vascular events than LDL-C or non-HDL cholesterol. Finally, there are at least 7 distinct subclasses of LDL of different particle sizes and several recent studies have suggested that LDL subfraction distribution, especially the presence of increased levels of small, dense LDL particles, aid in the prediction of cardiac heart disease risk. Further studies will clarify the clinical circumstances that justify lipoprotein analysis and how to best use the information taken from these new indices in the management of our patients

Predictive Factors for Positive Coronary Angiography and the Role of Early Intervention After Out-of-Hospital Cardiac Arrest

Background: In recent years, there has been considerable research in the field of post-resuscitation care. Recent guidelines recommend early coronary angiography and percutaneous coronary intervention (PCI) as the best strategy in survivors of out-of-hospital cardiac arrest (OOHCA) with ST elevation myocardial infarction (STEMI). However, there are no decisive data for patients who do not exhibit clinical and ECG criteria suggestive of STEMI. We sought to review current evidence regarding the predictive factors of positive coronary angiography and the role of early PCI in an OOHCA setting.Methods & Results: Between 1995 and 2014, we identified 35 studies reporting on adult survivors of OOHCA who underwent coronary angiography and PCI. In total, there are over 16,000 patients included in reported series of resuscitated OOHCA victims who have undergone coronary angiography and PCI when indicated. PCI was successful in 92% (51% - 100%) of the attempted cases. The survival rate was 64% (22% - 88%) with a satisfactory neurological outcome at follow-up that varied from 47% to 96%. As the survival benefit seems to be time dependent, the selection of which patients are candidates for early PCI is under considerable research. Predictive factors for positive coronary angiography and outcome were ventricular fibrillation, history of coronary heart disease and diabetes mellitus, ST elevation on ECG, male gender, and intact brain stem functions. Negative predictive factors were normal ECG on admission or the presence of plain repolarization abnormalities, and loss of brain stem functions.Conclusions: Early coronary angiography and PCI is a promising management strategy in the OOHCA setting. As there is evidence that the survival benefit from PCI is time dependent, the research is still ongoing in identifying which patients would benefit most from an aggressive revascularization approach

Pollution risk and life insurance decisions: microgeographic evidence from the United Kingdom

Recent research documents that exposure to air pollution can trigger various behavioral reactions. This article presents novel empirical evidence on the causal effect of pollution risk on life insurance decisions. We create a unique dataset by linking microgeographic air quality information to the confidential UK Wealth and Assets Survey. We identify an inverse N-shape relationship between pollution risk and life insurance adoption by exploiting the orthogonal variations in meteorological conditions. Over a given range above a threshold of exposure, rising pollution is associated with rising demand for life insurance, whereas at lower than the threshold levels of pollution, higher exposure risk reduces demand for insurance. Our findings indicate—for the first time—a nonlinear relationship between local pollution risk and life insurance demand

Predictive Factors for Positive Coronary Angiography and the Role of Early Intervention After Out-of-Hospital Cardiac Arrest

Background: In recent years, there has been considerable research in the field of post-resuscitation care. Recent guidelines recommend early coronary angiography and percutaneous coronary intervention (PCI) as the best strategy in survivors of out-of-hospital cardiac arrest (OOHCA) with ST elevation myocardial infarction (STEMI). However, there are no decisive data for patients who do not exhibit clinical and ECG criteria suggestive of STEMI. We sought to review current evidence regarding the predictive factors of positive coronary angiography and the role of early PCI in an OOHCA setting.Methods & Results: Between 1995 & 2014, we identified 35 studies reporting on adult survivors of OOHCA who underwent coronary angiography and PCI. In total, there are over 16,000 patients included in reported series of resuscitated OOHCA victims who have undergone coronary angiography and PCI when indicated. PCI was successful in 92% (51-100%) of the attempted cases. The survival rate was 64% (22% - 88%) with a satisfactory neurological outcome at follow-up that varied from 47-96%. As the survival benefit seems to be time dependent, the selection of which patients are candidates for early PCI is under considerable research. Predictive factors for positive coronary angiography and outcome were ventricular fibrillation, history of coronary heart disease and diabetes, ST elevation on ECG, male gender, and intact brain stem functions. Negative predictive factors were normal ECG on admission or plain repolarization abnormalities, and loss of brain stem functions.Conclusions: Early coronary angiography and PCI is a promising management strategy in the OOHCA setting. As there is evidence that the survival benefit from PCI is time dependent, the research is still ongoing in identifying which patients would benefit most from an aggressive revascularization approach

Inordinately Sluggish Coronary Artery Flow in an Angiographically Normal Coronary Artery

A 53-year-old male smoker, without any significant medical history was admitted via the emergency room to the cardiac care unit due to a single episode of unstable angina lasting for approximately 10 minutes. Over the last one year he admits to symptoms indicative of CCS class II effort angina. He had a positive exercise stress test a year earlier. On admission no ischemic ECG changes were noted. Cardiac enzymes were normal. Coronary angiography, performed the next day, revealed no significant atherosclerotic lesions, however an impressively sluggish flow was observed in the left anterior descending (LAD) coronary artery. The patient was discharged home the following day on full antianginal regimen, including aspirin, clopidogrel, nitrates, β-blocker and statin. At three months later the patient has remained free of symptoms

Spectroscopic Observations of Convective Patterns in the Atmospheres of Metal-Poor Stars

Convective line asymmetries in the optical spectrum of two metal-poor stars, Gmb1830 and HD140283, are compared to those observed for solar metallicity stars. The line bisectors of the most metal-poor star, the subgiant HD140283, show a significantly larger velocity span that the expectations for a solar-metallicity star of the same spectral type and luminosity class. The enhanced line asymmetries are interpreted as the signature of the lower metal content, and therefore opacity, in the convective photospheric patterns. These findings point out the importance of three-dimensional convective velocity fields in the interpretation of the observed line asymmetries in metal-poor stars, and in particular, urge for caution when deriving isotopic ratios from observed line shapes and shifts using one-dimensional model atmospheres. The mean line bisector of the photospheric atomic lines is compared with those measured for the strong Mg I b1 and b2 features. The upper part of the bisectors are similar, and assuming they overlap, the bottom end of the stronger lines, which are formed higher in the atmosphere, goes much further to the red. This is in agreement with the expected decreasing of the convective blue-shifts in upper atmospheric layers, and compatible with the high velocity redshifts observed in the chromosphere, transition region, and corona of late-type stars.Comment: 27 pages, LaTeX; 10 Figures (14 PostScript files); to be published in The Astrophysical Journa

Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma.

BACKGROUND: The chronic airway inflammation in severe eosinophilic asthma (SEA) suggests potential autoimmune aetiology with unidentified autoantibodies analogous to myeloperoxidase (MPO) in ANCA-positive EGPA (eosinophilic granulomatosis with polyangiitis). Previous research has shown that oxidative post-translational modification (oxPTM) of proteins is an important mechanism by which autoantibody responses may escape immune tolerance. Autoantibodies to oxPTM autoantigens in SEA have not previously been studied. METHODS: Patients with EGPA and SEA were recruited as well as healthy control participants. Autoantigen agnostic approach: Participant serum was incubated with slides of unstimulated and PMA-stimulated neutrophils and eosinophils, and autoantibodies to granulocytes were identified by immunofluorescence with anti-human IgG FITC antibody. Target autoantigen approach: Candidate proteins were identified from previous literature and FANTOM5 gene set analysis for eosinophil expressed proteins. Serum IgG autoantibodies to these proteins, in native and oxPTM form, were detected by indirect ELISA. RESULTS: Immunofluorescence studies showed that serum from patients with known ANCA stained for IgG against neutrophils as expected. In addition, serum from 9 of 17 tested SEA patients stained for IgG to PMA-stimulated neutrophils undergoing NETosis. Immunofluorescent staining of eosinophil slides was evident with serum from all participants (healthy and with eosinophilic disease) with diffuse cytoplasmic staining except for one SEA individual in whom subtle nuclear staining was evident. FANTOM5 gene set analysis identified TREM1 (triggering receptor expressed on myeloid cells 1) and IL-1 receptor 2 (IL1R2) as eosinophil-specific targets to test for autoantibody responses in addition to MPO, eosinophil peroxidase (EPX), and Collagen-V identified from previous literature. Indirect ELISAs found high concentrations of serum autoantibodies to Collagen-V, MPO, and TREM1 in a higher proportion of SEA patients than healthy controls. High concentrations of serum autoantibodies to EPX were evident in serum from both healthy and SEA participants. The proportion of patients with positive autoantibody ELISAs was not increased when examining oxPTM compared to native proteins. DISCUSSION: Although none of the target proteins studied showed high sensitivity for SEA, the high proportion of patients positive for at least one serum autoantibody shows the potential of more research on autoantibody serology to improve diagnostic testing for severe asthma. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier, NCT04671446

Deleterious Effects of Cold Air Inhalation on Coronary Physiological Indices in Patients With Obstructive Coronary Artery Disease

Background Cold air inhalation during exercise increases cardiac mortality, but the pathophysiology is unclear. During cold and exercise, dual‐sensor intracoronary wires measured coronary microvascular resistance (MVR) and blood flow velocity (CBF), and cardiac magnetic resonance measured subendocardial perfusion. Methods and Results Forty‐two patients (62±9 years) undergoing cardiac catheterization, 32 with obstructive coronary stenoses and 10 without, performed either (1) 5 minutes of cold air inhalation (5°F) or (2) two 5‐minute supine‐cycling periods: 1 at room temperature and 1 during cold air inhalation (5°F) (randomized order). We compared rest and peak stress MVR, CBF, and subendocardial perfusion measurements. In patients with unobstructed coronary arteries (n=10), cold air inhalation at rest decreased MVR by 6% (P=0.41), increasing CBF by 20% (P<0.01). However, in patients with obstructive stenoses (n=10), cold air inhalation at rest increased MVR by 17% (P<0.01), reducing CBF by 3% (P=0.85). Consequently, in patients with obstructive stenoses undergoing the cardiac magnetic resonance protocol (n=10), cold air inhalation reduced subendocardial perfusion (P<0.05). Only patients with obstructive stenoses performed this protocol (n=12). Cycling at room temperature decreased MVR by 29% (P<0.001) and increased CBF by 61% (P<0.001). However, cold air inhalation during cycling blunted these adaptations in MVR (P=0.12) and CBF (P<0.05), an effect attributable to defective early diastolic CBF acceleration (P<0.05) and associated with greater ST‐segment depression (P<0.05). Conclusions In patients with obstructive coronary stenoses, cold air inhalation causes deleterious changes in MVR and CBF. These diminish or abolish the normal adaptations during exertion that ordinarily match myocardial blood supply to demand

Gene expression profile of circulating tumor cells in breast cancer by RT-qPCR

<p>Abstract</p> <p>Background</p> <p>Circulating tumor cells (CTCs) have been associated with prognosis especially in breast cancer and have been proposed as a liquid biopsy for repeated follow up examinations. Molecular characterization of CTCs is difficult to address since they are very rare and the amount of available sample is very limited.</p> <p>Methods</p> <p>We quantified by RT-qPCR <it>CK-19, MAGE-A3, HER-2, TWIST1, hTERT α+β+</it>, and <it>mammaglobin </it>gene transcripts in immunomagnetically positively selected CTCs from 92 breast cancer patients, and 28 healthy individuals. We also compared our results with the CellSearch system in 33 of these patients with early breast cancer.</p> <p>Results</p> <p>RT-qPCR is highly sensitive and specific and can detect the expression of each individual gene at the one cell level. None of the genes tested was detected in the group of healthy donors. In 66 operable breast cancer patients, <it>CK-19 </it>was detected in 42.4%, <it>HER-2 </it>in 13.6%, <it>MAGE-A3 </it>in 21.2%, <it>hMAM </it>in 13.6%, <it>TWIST-1 </it>in 42.4%, and <it>hTERT α+β+ </it>in 10.2%. In 26 patients with verified metastasis, <it>CK-19 </it>was detected in 53.8%, <it>HER-2 </it>in 19.2%, <it>MAGE-A3 </it>in 15.4%, <it>hMAM </it>in 30.8%, <it>TWIST-1 </it>in 38.5% and <it>hTERT </it>α⁺β⁺in 19.2%. Our preliminary data on the comparison between RT-qPCR and CellSearch in 33 early breast cancer patients showed that RT-qPCR gives more positive results in respect to CellSearch.</p> <p>Conclusions</p> <p>Molecular characterization of CTCs has revealed a remarkable heterogeneity of gene expression between breast cancer patients. In a small percentage of patients, CTCs were positive for all six genes tested, while in some patients only one of these genes was expressed. The clinical significance of these findings in early breast cancer remains to be elucidated when the clinical outcome for these patients is known.</p

Reducing Barriers for Implementation of Immediate CPR with Chest Compressions Alone

&nbsp; It is well known that out-of-hospital sudden cardiac death is a leading public health problem. In the absence of early defibrillation, survival rates of patients with out-of-hospital cardiac arrest are dismal and have remained essentially unchanged. The guidelines advocate the same approach for 2 entirely different pathophysiological conditions: respiratory arrest in which severe arterial hypoxia and hypotension eventually lead to secondary cardiac arrest, and primary cardiac arrest in which the arterial blood is fully saturated with oxygen at the time of the arrest. Cardiopulmonary resuscitation (CPR) is traditionally defined as chest compressions plus ventilations. The need for chest compressions is unquestionable, while the need for mouth-to-mouth ventilations for cardiac arrest has been questioned. Recent observational studies underline the paramount role of chest compressions in an alternative way of CPR, compression only CPR. Public education and training in compression only CPR is much simpler. Compression only CPR may significantly increase bystander-initiated resuscitation efforts and thereby give patients a better chance of survival, given the reluctance of lay people to provide mouth to mouth rescue breaths. In view of the above, the principal question is, what barriers are delaying the guidelines from recommending compression only CPR? Perhaps the major problem is the difficulty to change the paradigm. For decades, the "ABCs" (airway, breathing, and circulation) have been advocated for bystander basic life support, making it extremely difficult to transform the so ingrained in the popular understanding "ABC" to "AC"