Cardiac Resynchronization Therapy in the Cardiorenal Syndrome

The cardiorenal syndrome (CRS) is a complex clinical syndrome in which dysfunction of either the heart or the kidneys affects the functioning of the other organ system. Many therapies used in heart failure have further detrimental effects on renal function. Cardiac resynchronization therapy (CRT) is a relatively new form of device therapy that reduces morbidity and mortality in patients with heart failure. This review will discuss the effects of CRT on renal function in patients with CRS, the impact of baseline renal function on response to CRT, and potential risks associated with CRT in this unique population

The Hard X-Ray View of Reflection, Absorption, and the Disk-Jet Connection in the Radio-Loud AGN 3C 33

We present results from Suzaku and Swift observations of the nearby radio galaxy 3C 33, and investigate the nature of absorption, reflection, and jet production in this source. We model the 0.5-100 keV nuclear continuum with a power law that is transmitted either through one or more layers of pc-scale neutral material, or through a modestly ionized pc-scale obscurer. The standard signatures of reflection from a neutral accretion disk are absent in 3C 33: there is no evidence of a relativistically blurred Fe K$\alpha$ emission line, and no Compton reflection hump above 10 keV. We find the upper limit to the neutral reflection fraction is R<0.41 for an e-folding energy of 1 GeV. We observe a narrow, neutral Fe K$\alpha$ line, which is likely to originate at least 2,000 R_s from the black hole. We show that the weakness of reflection features in 3C 33 is consistent with two interpretations: either the inner accretion flow is highly ionized, or the black-hole spin configuration is retrograde with respect to the accreting material.Comment: 12 pages, 11 figures, 4 tables. Accepted for publication in Ap

Optical Spectroscopy Of X-Ray Sources In The Extended Chandra Deep Field South

We present the first results of our optical spectroscopy program aimed to provide redshifts and identifications for the X-ray sources in the Extended Chandra Deep Field South. A total of 339 sources were targeted using the IMACS spectrograph at the Magellan telescopes and the VIMOS spectrograph at the VLT. We measured redshifts for 186 X-ray sources, including archival data and a literature search. We find that the active galactic nucleus (AGN) host galaxies have on average redder rest-frame optical colors than nonactive galaxies, and that they live mostly in the "green valley." The dependence of the fraction of AGNs that are obscured on both luminosity and redshift is confirmed at high significance and the observed AGN spatial density is compared with the expectations from existing luminosity functions. These AGNs show a significant difference in the mid-IR to X-ray flux ratio for obscured and unobscured AGNs, which can be explained by the effects of dust self-absorption on the former. This difference is larger for lower luminosity sources, which is consistent with the dust opening angle depending on AGN luminosity.National Aeronautics and Space Administration PF8-90055, NAS8-03060NSF AST0407295Spitzer JPL RSA1288440Natural Science and Engineering Research Council of Canada (NSERC)National Academy of SciencesNASA/INTEGRAL NNG05GM79GAstronom

Maximum tolerable dose of cyclophosphamide and azathioprine in Pakistani patients with primary renal disease

Objective: The immunosuppressive regimens, at present, mainly rely on western guidelines that were derived from studies conducted in western populations. No such study exists for South Asian population, which is home to almost two billion people different in both genetics and environment from west. Locally derived thresholds for side effects markedly different from western figures may warrant re-adjustment of current local immunosuppressive regimens that are at present based largely on western guidelines. In order to define optimum dose for Cyclophosphamide (CYC) and Azathioprine (AZA) based immunosuppressive therapy, we conducted this study to find out maximum tolerable doses of azathioprine (AZA) and cyclophosphamide (CYC) beyond which neutropenia and thrombocytepenia are most likely to occur in patients with primary renal pathology.METHOD: Patients with systemic vasculitis and idiopathic glomerulonephritis who were on CYC and AZA were identified through review of medical records at a tertiary care hospital in Pakistan (The Aga Khan University Hospital, Karachi). Patients were categorized under three principal diagnosis i.e. systemic lupus erythematosus (SLE), primary (idiopathic) glomerulonephritis (GN) and Wegener\u27s granulomatosis (WG). The Receiver Operating Curve (ROC) was used to calculate the maximum tolerable dose for both CYC and AZA.Results: We identified 94 patients aged 6-82 years (median 44.5 years) with primary renal disease (Wegener\u27s granulomatosis n=13, Systemic lupus erythematosis n=62 and idiopathic glomerulonephritis n=19) who received CYC or AZA. Of these 94 patients, 36.2% (n=34) received CYC and 63.8% (n=60) received AZA. The mean dose of CYC was 1.54 +/- 0.50 mg/kg of body weight (range: 0.77-2.93). The mean dose of AZA was 1.64 +/- 0.59 mg/kg of body weight (range: 0.47-2.97). The maximum tolerable doses calculated for CYC and AZA were 1.25 mg/kg and 1.30 mg/kg of body weight respectively. The maximum tolerable dose for CYC and AZA among males could not be calculated, because of insufficient number of patients who developed neutropenia and thrombocytopenia. The maximum tolerable doses for CYC and AZA among females were 1.34 mg/kg and 1.03 mg/kg of body weight respectively. Also we found out that AZA was relatively more likely to cause neutropenia and thrombocytopenia (p=0.07).CONCLUSION: We thereby recommend that CYC should be initiated at a dose no more than 1 mg/kg of body weight and AZA at an initial dose of 0.75-1.0 mg/kg of body weight. The dose may be adjusted later on the basis of clinical response and laboratory reports

Abstract 219: Use of Machine Learning Models to Identify Atherosclerotic Cardiovascular Disease Patients at Very High Risk for Future Events in a Multi-state Health Care System

Background: In the 2018 AHA/ACC Blood Cholesterol Guideline, it is recommended that ASCVD patients be classified as very high-risk (VHR) vs not-VHR (NVHR) to guide treatment decisions. This has important implications for ezetimibe and PCSK9 inhibitor eligibility. We aimed to develop a tool that could assist in more easily identifying VHR patients based on machine learning (ML) techniques. This approach offers a powerful, assumption-free alternative to conventional methods, such as logistic regression, to identify potential interactions among risk factors while incorporating the hierarchy of interaction among variables. Method: We used EHR-derived ICD-10 codes to identify patients within our health system with ASCVD. VHR was defined by ≥2 major ASCVD events (ACS ≤12 months, history of MI \u3e12 months, ischemic stroke, or symptomatic PAD) or 1 major ASCVD event and ≥2 high-risk conditions (age ≥65, diabetes, hypertension, smoking, heterozygous familial hypercholesterolemia, CKD, CHF, persistently elevated LDL-C ≥100 mg/dl, or prior CABG/PCI). Patients not meeting these criteria were classified as NVHR. We randomly assigned patients into a training set and a testing set. Classification and regression tree (CART) modeling was performed on the training set and validated on the testing set. The results were compared with a random forest model. Variables in both models included age, sex, race, ethnicity, and each of the VHR criteria above. The primary outcome for both models was VHR classification. Performance of the two models were compared using area under the curve (AUC). Result: A total of 180,669 ASCVD patients were identified in 2018: 104,123 (58%) were VHR and 76,546 (42%) were NVHR. Mean age and sex were 73.1±11.9 years, 55% male and 70.1±13.4 years, 54% male for the VHR and NVHR groups, respectively. Half the population was randomly selected as the training dataset (n=90,334) and the other half was used as the testing dataset (n=90,335). Both CART and random forest models identified recent ACS, ischemic stroke, hypertension, PAD, and history of MI as the top five predictors of VHR status. Ninety-six percent of patients with recent ACS were classified as VHR. Among patients with no recent ACS, 95% were classified as VHR if they had a stroke and hypertension. Among patients with no ACS or stroke, 89% were classified as VHR if they had PAD. Finally, among patients with no ACS, stroke or PAD, 90% were classified as VHR if they had a history of MI. The misclassification rate of the CART model on the testing set was 4.3%. The AUC for the CART and random forest models was 0.949 and 0.968, respectively. Conclusion: Both ML methods were highly predictive of VHR status among those with ASCVD. Use of this approach affords a simplified means to drive clinical decision making at the point of care

The Sudden Death of the Nearest Quasar

Galaxy formation is significantly modulated by energy output from supermassive black holes at the centers of galaxies which grow in highly efficient luminous quasar phases. The timescale on which black holes transition into and out of such phases is, however, unknown. We present the first measurement of the shutdown timescale for an individual quasar using X-ray observations of the nearby galaxy IC 2497, which hosted a luminous quasar no more than 70,000 years ago that is still seen as a light echo in `Hanny's Voorwerp', but whose present-day radiative output is lower by at least 2 and more likely by over 4 orders of magnitude. This extremely rapid shutdown provides new insights into the physics of accretion in supermassive black holes, and may signal a transition of the accretion disk to a radiatively inefficient state.Comment: 4 pages, 2 figures. Astrophysical Journal Letters, in pres