Contrast-Induced Acute Kidney Injury

Cardiac angiography and coronary/vascular interventions depend on iodinated contrast media and consequently pose the risk of contrast-induced acute kidney injury (AKI). This is an important complication that accounts for a significant number of cases of hospital-acquired renal failure, with adverse effects on prognosis and health care costs. The epidemiology and pathogenesis of contrast-induced AKI, baseline renal function measurement, risk assessment, identification of high-risk patients, contrast medium use, and preventive strategies are discussed in this report. An advanced algorithm is suggested for the risk stratification and management of contrast-induced AKI as it relates to patients undergoing cardiovascular procedures. Contrast-induced AKI is likely to remain a significant challenge for cardiologists in the future because the patient population is aging and chronic kidney disease and diabetes are becoming more common

Evaluation and treatment of coronary artery disease in patients with end-stage renal disease

Evaluation and treatment of coronary artery disease in patients with end-stage renal disease. Patients with end-stage renal disease (ESRD) are at increased risk of death from coronary artery disease (CAD). The metabolic milieu that results from renal dysfunction appears to accelerate the atherosclerotic process by decades in patients with ESRD. The extremely high prevalence of atherosclerosis in patients with ESRD mandates risk factor identification and treatment. Traditionally, CAD in this patient population has been treated conservatively. Analysis of large databases has highlighted the scope and complexity of this problem; nonetheless, there is a paucity of randomized, controlled trials of CAD in patients with ESRD. In this paper the following issues related to evaluation and treatment of patients with chronic kidney disease are addressed: (1) optimal CAD risk management; (2) evaluation for CAD in patients with ESRD, including the identification of coronary calcification; (3) treatment of CAD with medical therapy and revascularization; (4) relative merits of percutaneous coronary intervention versus bypass surgery. In general, an aggressive approach to medical management of CAD is warranted, even in the setting of subclinical CAD. A low threshold for diagnostic testing should be employed in patients with ESRD. When significant CAD is identified, ESRD patients appear to benefit more from revascularization compared to conservative medical management. Thus, if clinically reasonable, patients with ESRD and CAD should be managed aggressively to improve survival and reduce the incidence of future cardiac events

Cardiorenal Syndromes: Pathophysiology to Prevention

There is a strong association between both acute and chronic dysfunction of the heart and kidneys with respect to morbidity and mortality. The complex interrelationships of longitudinal changes in both organ systems have been difficult to describe and fully understand due to a lack of categorization of the common clinical scenarios where these phenomena are encountered. Thus, cardiorenal syndromes (CRSs) have been subdivided into five syndromes which represent clinical vignettes in which both the heart and the kidney are involved in bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress. Types 1 and 2 involve acute and chronic cardiovascular disease (CVD) scenarios leading to acute kidney injury (AKI) or accelerated chronic kidney disease (CKD). Types 3 and 4 describe AKI and CKD, respectively, leading primarily to heart failure, although it is possible that acute coronary syndromes, stroke, and arrhythmias could be CVD outcomes in these forms of CRS. Finally, CRSs type 5 describe a systemic insult to both heart and the kidneys, such as sepsis, where both organs are injured simultaneously in persons with previously normal heart and kidney function at baseline. Both blood and urine biomarkers, including the assessment of catalytic iron, a critical element to the generation of oxygen-free radicals and oxidative stress, are reviewed in this paper

The Multitude of Molecular Hydrogen Knots in the Helix Nebula

We present HST/NICMOS imaging of the H_2 2.12 \mu m emission in 5 fields in the Helix Nebula ranging in radial distance from 250-450" from the central star. The images reveal arcuate structures with their apexes pointing towards the central star. Comparison of these images with comparable resolution ground based images reveals that the molecular gas is more highly clumped than the ionized gas line tracers. From our images, we determine an average number density of knots in the molecular gas ranging from 162 knots/arcmin^2 in the denser regions to 18 knots/arcmin^2 in the lower density outer regions. Using this new number density, we estimate that the total number of knots in the Helix to be ~23,000 which is a factor of 6.5 larger than previous estimates. The total neutral gas mass in the Helix is 0.35 M_\odot assuming a mass of \~1.5x10^{-5} M_\odot for the individual knots. The H_2 intensity, 5-9x10^{-5} erg s^{-1} cm^{-2} sr^{-1}, remains relatively constant with projected distance from the central star suggesting a heating mechanism for the molecular gas that is distributed almost uniformly in the knots throughout the nebula. The temperature and H_2 2.12 \mu m intensity of the knots can be approximately explained by photodissociation regions (PDRs) in the individual knots; however, theoretical PDR models of PN under-predict the intensities of some knots by a factor of 10.Comment: 26 pages, 3 tables, 10 figures; AJ accepte

Statistical Analysis Methods Applied to Early Outpatient COVID-19 Treatment Case Series Data

When confronted with a public health emergency, significant innovative treatment protocols can sometimes be discovered by medical doctors at the front lines based on repurposed medications. We propose a statistical framework for analyzing the case series of patients treated with such new protocols, that enables a comparison with our prior knowledge of expected outcomes, in the absence of treatment. The goal of the proposed methodology is not to provide a precise measurement of treatment efficacy, but to establish the existence of treatment efficacy, in order to facilitate the binary decision of whether the treatment protocol should be adopted on an emergency basis. The methodology consists of a frequentist component that compares a treatment group against the probability of an adverse outcome in the absence of treatment, and calculates an efficacy threshold that has to be exceeded by this probability, in order to control the corresponding p-value and reject the null hypothesis. The efficacy threshold is further adjusted with a Bayesian technique, in order to also control the false positive rate. A random selection bias threshold is then calculated from the efficacy threshold to control for random selection bias. Exceeding the efficacy threshold establishes the existence of treatment efficacy by the preponderance of evidence, and exceeding the more demanding random selection bias threshold establishes the existence of treatment efficacy by the clear and convincing evidentiary standard. The combined techniques are applied to case series of high-risk COVID-19 outpatients that were treated using the early Zelenko protocol and the more enhanced McCullough protocol

The XO Planetary Survey Project - Astrophysical False Positives

Searches for planetary transits find many astrophysical false positives as a by-product. There are four main types analyzed in the literature: a grazing-incidence eclipsing binary star, an eclipsing binary star with a small radius companion star, a blend of one or more stars with an unrelated eclipsing binary star, and a physical triple star system. We present a list of 69 astrophysical false positives that had been identified as candidates of transiting planets of the on-going XO survey. This list may be useful in order to avoid redundant observation and characterization of these particular candidates independently identified by other wide-field searches for transiting planets. The list may be useful for those modeling the yield of the XO survey and surveys similar to it. Subsequent observations of some of the listed stars may improve mass-radius relations, especially for low-mass stars. From the candidates exhibiting eclipses, we report three new spectroscopic double-line binaries and give mass function estimations for 15 single lined spectroscopic binaries.Comment: 13 pages, 4 figures, accepted to ApJ

A Gas Giant Circumbinary Planet Transiting the F Star Primary of the Eclipsing Binary Star KIC 4862625 and the Independent Discovery and Characterization of the two transiting planets in the Kepler-47 System

We report the discovery of a transiting, gas giant circumbinary planet orbiting the eclipsing binary KIC 4862625 and describe our independent discovery of the two transiting planets orbiting Kepler-47 (Orosz et al. 2012). We describe a simple and semi-automated procedure for identifying individual transits in light curves and present our follow-up measurements of the two circumbinary systems. For the KIC 4862625 system, the 0.52+/-0.018 RJup radius planet revolves every ~138 days and occults the 1.47+/-0.08 MSun, 1.7 +/-0.06 RSun F8 IV primary star producing aperiodic transits of variable durations commensurate with the configuration of the eclipsing binary star. Our best-fit model indicates the orbit has a semi-major axis of 0.64 AU and is slightly eccentric, e=0.1. For the Kepler-47 system, we confirm the results of Orosz et al. (2012). Modulations in the radial velocity of KIC 4862625A are measured both spectroscopically and photometrically, i.e. via Doppler boosting, and produce similar results.Comment: 40 pages, 17 figure

Mortality benefit of angiotensin-converting enzyme inhibitors after cardiac events in patients with end-stage renal disease

Hypothesis/introduction. The risks and benefits of angiotensin-converting enzyme (ACE) inhibitors in patients with end-stage renal disease (ESRD) after cardiac events are unknown. We sought to determine the independent effect of ACE inhibitors (ACE-I) on long-term mortality in ESRD patients after cardiac events. Materials and methods. We analysed a prospective coronary care unit registry and identified 527 ESRD patients, 368 with complete data on medications prescribed, over eight years at a single, tertiary centre. Results. The overall mean age was 64.4±13.8 years with 54.9% men, and 59.2% African-American. A total of 143/386 (37.0%) were prescribed ACE-I during the hospital stay for cardiac reasons, including congestive heart failure (CHF) 52.8% and acute coronary syndromes (ACS) 47.2%. There were no significant differences in the rates of hypotension or arrhythmias in those who were treated with ACE-I versus those who were not. Survival analysis over three years, adjusted for known confounders, demonstrated a 37% reduction in all-cause mortality in those who received ACE-I, (p=0.0145). Conclusions. In the setting of coronary care unit admission for CHF and ACS, ESRD patients selected for ACE-I, did not have increased rates of adverse haemodynamic or arrhythmic complications. The use of ACE-I conferred an independent mortality reduction over long-term follow-up

Unraveling the Helix Nebula: Its Structure and Knots

Through HST imaging of the inner part of the main-ring of the Helix Nebula together with CTIO 4-m images of the fainter outer parts, we have an unprecedented-quality view of the nearest bright planetary nebula. These images have allowed determination that the main-ring of the nebula is composed of an inner-disk of about 499\arcsec diameter (0.52 pc) surrounded by an outer-ring (in reality a torus) of 742\arcsec diameter (0.77 pc) whose plane is highly inclined to the plane of the disk. This outer-ring is surrounded by an outermost-ring of 1500\arcsec (1.76 pc) diameter which is flattened on the side colliding with the ambient interstellar medium. The inner-disk has an extended distribution of low density gas along its rotational axis of symmetry and the disk is optically thick to ionizing radiation, as is the outer-ring. Published radial velocities of the knots provides support for the two-component structure of the main-ring of the nebula and to the idea that the knots found there are expanding along with the nebular material from which it recently originated. There is a change in the morphology of the knots as a function of the distance from the local ionization front. This supports a scenario in which the knots are formed in or near the ionization front and are then sculpted by the stellar radiation from the central star as the ionization front advances beyond them.Comment: 30 pages, 20 figures, many figures have reduce fidelity for astroph preprint. Note: URLs in preprint were change

Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl

Background: A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2–related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.<p></p> Methods and Results: We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min−1 1.73 m−2) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl– and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events.<p></p> Conclusions: Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.<p></p&gt