tbuckley/cabot-search huggingface dataset:
Association of Primary Care Physician Supply With Population Mortality in the United States, 2005-2015
Authors: Sanjay Basu, Seth A. Berkowitz, Robert L. Phillips, Asaf Bitton, Bruce E. Landon, Russell S. Phillips
Journal: JAMA Internal Medicine (2019)

Recent US health care reforms incentivize improved population health outcomes and primary care functions. It remains unclear how much improving primary care physician supply can improve population health, independent of other health care and socioeconomic factors.To identify primary care physician supply changes across US counties from 2005-2015 and associations between such changes and population mortality.This epidemiological study evaluated US population data and individual-level claims data linked to mortality from 2005 to 2015 against changes in primary care and specialist physician supply from 2005 to 2015. Data from 3142 US counties, 7144 primary care service areas, and 306 hospital referral regions were used to investigate the association of primary care physician supply with changes in life expectancy and cause-specific mortality after adjustment for health care, demographic, socioeconomic, and behavioral covariates. Analysis was performed from March to July 2018.Age-standardized life expectancy, cause-specific mortality, and restricted mean survival time.Primary care physician supply increased from 196 014 physicians in 2005 to 204 419 in 2015. Owing to disproportionate losses of primary care physicians in some counties and population increases, the mean (SD) density of primary care physicians relative to population size decreased from 46.6 per 100 000 population (95% CI, 0.0-114.6 per 100 000 population) to 41.4 per 100 000 population (95% CI, 0.0-108.6 per 100 000 population), with greater losses in rural areas. In adjusted mixed-effects regressions, every 10 additional primary care physicians per 100 000 population was associated with a 51.5-day increase in life expectancy (95% CI, 29.5-73.5 days; 0.2% increase), whereas an increase in 10 specialist physicians per 100 000 population corresponded to a 19.2-day increase (95% CI, 7.0-31.3 days). A total of 10 additional primary care physicians per 100 000 population was associated with reduced cardiovascular, cancer, and respiratory mortality by 0.9% to 1.4%. Analyses at different geographic levels, using instrumental variable regressions, or at the individual level found similar benefits associated with primary care supply.Greater primary care physician supply was associated with lower mortality, but per capita supply decreased between 2005 and 2015. Programs to explicitly direct more resources to primary care physician supply may be important for population health.
ECG Response: December 24/31, 2013
Authors: Philip Podrid
Journal: Circulation (2013)

A 64-year-old man presents to the emergency room with a history of 2 hours of substernal chest discomfort that radiates to his lower jaw and left arm.The discomfort is associated with severe diaphoresis.Physical examination demonstrates a blood pressure of 150/90 mm Hg, bibasilar rales, and an S4.Initial cardiac biomarkers are normal.However, based on the clinical presentation and the initial ECG (ECG A) the patient undergoes an urgent cardiac catheterization and an intervention is performed.On the following day a second ECG is obtained (ECG B).
Abstract 532: Titin’s N2B Element is Critical to Cardiac Mechanotransduction during Volume Overload, but not Pressure Overload
Authors: Joshua Strom, Mathew Bull, Chandra Saripalli, Jochen Gohlke, Michael Gotthardt, Henk Granzier
Journal: Circulation Research (2018)

The heart senses and responds to changes in mechanical loading conditions by initiating signaling events to produce structural and functional remodeling through a process known as mechanotransduction. Within cardiac myocytes, the giant protein titin has been implicated as a key player in the conversion of mechanical stimuli into downstream signaling events as part of the adaptive responses of mechanotransduction. The N2B element within the extensible I-band of titin has been proposed to be a stretch sensor and signaling hot spot important to titin’s role as a mechanosensor. To investigate the role of the N2B element in mechanotransduction, N2B knockout (N2BKO) mice were subjected to cardiac pressure overload by transverse aortic constriction (TAC) or volume overload by aortocaval fistula (ACF). Following 4 weeks TAC, WT mice respond with 37% LV hypertrophy (4.0 ± 0.1 mg/gBW for TAC vs 2.9 ± 0.1 mg/gBW for sham) compared to 51% (3.8 ± 0.1 mg/gBW for TAC vs 2.5 ± 0.1 mg/gBW for sham) in N2BKO. In contrast, N2BKO mice demonstrated a severe lack of a hypertrophic response following 1-week ACF with 26% (4.0 ± 0.1 mg/gBW for ACF vs 3.1 ± 0.1 mg/gBW for sham) LV hypertrophy in WT compared to -2% (2.8 ± 0.1 mg/gBW for ACF vs 2.8 ± 0.1 mg/gBW for sham) in N2BKO. Additionally, while there was no incidence of mortality in WT mice subjected to ACF, approximately 36% (5 of 14) of N2BKO mice died within 1 week following ACF. Western blot analysis of canonical hypertrophy signaling kinases revealed no differences between WT and N2BKO mice at baseline or 1 week post-ACF. Four-and-a half LIM domains 1 and 2 (FHL1 and FHL2) have previously been shown to localize to the N2B element and FHL1 has been linked to mechanotransduction in TAC. In N2BKO, FHL1 protein is expressed at levels comparable to WT in both TAC and ACF; however, FHL2 protein levels are reduced by ~98% compared to WT (1.00 ± 0.26 for WT vs 0.02 ± 0.01% for N2BKO). These data indicate that while the N2B element is not required for mechanotransduction in pressure overload of the LV, it is critical for mechanosensing and the adaptive hypertrophy response during volume overload. FHL2 is an attractive candidate as a link between titin’s N2B element and the hypertrophy response following ACF and further work will critical examine its involvement.
Intestinal insulin/IGF1 signalling through FoxO1 regulates epithelial integrity and susceptibility to colon cancer
Authors: A. L. Ostermann, C. M. Wunderlich, L. Schneiders, M. C. Vogt, M. A. Woeste, B. F. Belgardt, C. M. Niessen, B. Martiny, A. C. Schauss, P. Frommolt, A. Nikolaev, N. Hövelmeyer, R. C. Sears, P. J. Koch, D. Günzel, J. C. Brüning, F. T. Wunderlich
Journal: Nature Metabolism (2019)
A Quantile-Based g-Computation Approach to Addressing the Effects of Exposure Mixtures
Authors: Alexander P. Keil, Jessie P. Buckley, Katie M. O’Brien, Kelly K. Ferguson, Shanshan Zhao, Alexandra J. White
Journal: Environmental Health Perspectives (2020)

Background: Exposure mixtures frequently occur in data across many domains, particularly in the fields of environmental and nutritional epidemiology. Various strategies have arisen to answer questions about exposure mixtures, including methods such as weighted quantile sum (WQS) regression that estimate a joint effect of the mixture components. Objectives: We demonstrate a new approach to estimating the joint effects of a mixture: quantile g-computation. This approach combines the inferential simplicity of WQS regression with the flexibility of g-computation, a method of causal effect estimation. We use simulations to examine whether quantile g-computation and WQS regression can accurately and precisely estimate the effects of mixtures in a variety of common scenarios. Methods: We examine the bias, confidence interval (CI) coverage, and bias–variance tradeoff of quantile g-computation and WQS regression and how these quantities are impacted by the presence of noncausal exposures, exposure correlation, unmeasured confounding, and nonlinearity of exposure effects. Results: Quantile g-computation, unlike WQS regression, allows inference on mixture effects that is unbiased with appropriate CI coverage at sample sizes typically encountered in epidemiologic studies and when the assumptions of WQS regression are not met. Further, WQS regression can magnify bias from unmeasured confounding that might occur if important components of the mixture are omitted from the analysis. Discussion: Unlike inferential approaches that examine the effects of individual exposures while holding other exposures constant, methods like quantile g-computation that can estimate the effect of a mixture are essential for understanding the effects of potential public health actions that act on exposure sources. Our approach may serve to help bridge gaps between epidemiologic analysis and interventions such as regulations on industrial emissions or mining processes, dietary changes, or consumer behavioral changes that act on multiple exposures simultaneously. https://doi.org/10.1289/EHP5838
Abstract 504: LAMP-2B Regulates Human Cardiomyocyte Function by Mediating Autophagosome-lysosome Fusion
Authors: Congwu Chi
Journal: Circulation Research (2018)

Autophagy plays a crucial role in cell homeostasis and function. Two types of autophagy have been well studied. Macroautophagy (referred to as autophagy hereafter) is mediated by double-membrane autophagosomes that enclose cytosolic cargoes, followed by fusion with late endosomes/lysosomes for degradation. Chaperone-mediated autophagy (CMA) is a process of chaperon-dependent selection of cytosolic proteins that are translocated into the lysosome for degradation. LAMP-2A, the A isoform of LAMP-2, is an essential receptor for CMA. However, alternative splicing of pre-LAMP-2 mRNA produces another two isoforms, LAMP-2B and LAMP-2C, with unclear functions. In non-cardiomyocytes, STX17 is required for autophagosome-lysosome fusion by interacting with SNAP29 and VAMP8. Whether cardiomyocytes (CMs) utilize the STX17-dependent mechanism to mediate autophagic fusion remains elusive. Using CMs derived from induced human pluripotent stem cells (hiPSC-CMs) and genome editing approaches, we identified previously undefined biological and molecular roles for LAMP-2B in the control of autophagosome-lysosome fusion. Remarkably, LAMP-2B functions independently of STX17. Instead, LAMP-2B interacts with ATG14 and VAMP8 through its C-terminal coiled-coil domain to promote autophagic fusion. Knockout of LAMP-2B in hiPSC-CMs decreased colocalization of ATG14 with VAMP8, and autophagosome-lysosome fusion. Forced expression of LAMP-2B in LAMP-2 deficient hiPSC-CMs restored autophagic signaling. In addition, LAMP-2B -deficient hiPSC-CMs recapitulated the metabolic and contractile defects observed in hiPSC-CMs derived from Danon patients. Danon disease represents a severe form of cardiomyopathy and has been associated with mutations in X-linked LAMP-2 gene. However, mechanisms by which LAMP-2 deficiency leads to cardiomyopathy are poorly understood. Given the similarity of phenotype between Danon and LAMP-2B knockout hiPSC-CMs, we conclude that LAMP-2B deficiency is sufficient and necessary to cause Danon cardiomyopathy. Therefore, our findings not only reveal a STX17-independent autophagic fusion mechanism mediated by LAMP-2B in human CMs, but also provide a molecular mechanism underlying Danon cardiomyopathy.
IgM Associated Light Chain (AL) Amyloidosis: Delineating Disease Biology with Clinical, Genomic and Bone Marrow Morphological Features
Authors: Surbhi Sidana, Rebecca L King, Patricia Greipp, Angela Dispenzieri, Rong He, Nidhi Tandon, Taxiarchis Kourelis, David S. Viswanatha, Eli Muchtar, Wilson I Gonsalves, Prashant Kapoor, Martha Q. Lacy, Francis K. Buadi, Suzanne R. Hayman, Nelson Leung, Robert A. Kyle, Shaji K. Kumar, Morie A. Gertz
Journal: Blood (2018)
THE HEMODYNAMIC IMPACT OF LEFT ATRIAL DYNAMICS DURING EXERCISE ON CLINICAL OUTCOME IN HEART FAILURE WITH PRESERVED, MID-RANGE, AND REDUCED EJECTION FRACTION
Authors: Tadafumi Sugimoto, Francesco Bandera, Greta Generati, Eleonora Alfonzetti, Valentina Labate, Marco Guazzi
Journal: Journal of the American College of Cardiology (2019)
STRESS CMR IN ABNORMAL LVEF: CLINICAL IMPACT AND COST EFFECTIVENESS
Authors: Yin Ge, Kevin Steel, Shuaib Abdullah, Scott Bingham, J. Ronald Mikolich, John Heitner, Andrew Arai, W. Patricia Bandettini, Amit Patel, Afshin Farzaneh-Far, Subha Raman, Chetan Shenoy, Jorge Gonzalez, Steve Leung, Dipan Shah, Victor Ferrari, Jeanette Schulz-Menger, Rory Hachamovitch, Matthias Stuber, Orlando Simonetti, Raymond Kwong
Journal: Journal of the American College of Cardiology (2019)
Abstract 19138: Thirty-day Readmission Following Transcatheter Aortic Valve Replacement is Common, Most Often Associated With Heart Failure and Infection, and Consumes Substantial Resources
Authors: Daniel J Lerner
Journal: Circulation (2015)

Introduction: Readmission within 30 days of hospitalization (30dRA) is increasingly used as a metric for quality of care. Transcatheter aortic valve replacement (TAVR) is also increasing, but 30dRA following TAVR is not well-understood. Hypothesis: The purpose of this study is to define the incidence, etiology, and resource utilization of 30dRA following TAVR. Methods: We used the ICD-9-CM code for TAVR (35.05) to identify patients who underwent TAVR and survived to discharge in 2012, in the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project’s State Independent Databases for 4 geographically distinct states: Florida, Massachusetts, New York, and Washington. The patients were divided into 2 groups: those with and without a 30dRA. Patients with a 30dRA for rehabilitation on the day of discharge were excluded. Approximately 8% of 30dRA were not captured because they occurred in the following year. Results: The incidence of 30dRA following TAVR was 20.2% (244/1210). The most common principal diagnoses for readmission were heart failure (21%), infection (17%), bleeding (11%), and dysrhythmia (7%). A total of 4.2% of patients died during the 30dRA. More than 60% required skilled care following discharge, and only 20% had a routine discharge to home or self-care. The Centers for Medicare and Medicaid Services (CMS) were the primary payer for 93.4% of 30dRA following TAVR. The mean length of stay for a 30dRA was 7.0 +/- 6.6 days. The mean charges for a 30dRA were $61,657 +/- $73,000. On univariate analysis, the number of chronic comorbidities (9.9 +/- 2.8 vs. 9.3+/- 2.8; P=0.002), length of index hospitalization (10.3 +/- 7.4 vs. 8.9 +/- 6.9; P=0.01), and non-routine discharge (83.1% vs. 72.6% P&lt;0.001) were associated with 30dRA. There was no significant difference in the mean age (83 years), gender makeup (50% female), racial makeup (19% non-White), and primary payer between patients who did and did not have a 30dRA. Conclusions: More than one in five patients undergoing TAVR is readmitted within 30 days of the procedure, most commonly for heart failure and infection. Future research should be directed toward identifying patients at risk for post-TAVR heart failure and infection prior to discharge, to reduce 30dRA.
LIPOPROTEIN(A) PROTEIN CONCENTRATION AND APOLIPOPROTEIN(A) KRINGLE IV ISOFORMS AMONG BLACK US ADULTS WITH AND WITHOUT PCSK9 LOSS-OF-FUNCTION VARIANTS
Authors: Matthew Mefford, Santica Marcovina, Vera Bittner, Mary Cushman, Todd Brown, Michael Farkouh, Keri Monda, J. Antonio Lopez, Paul Muntner, Robert Rosenson
Journal: Journal of the American College of Cardiology (2019)
TRANSFUSIONS, WITH OR WITHOUT CONCOMITANT BLEEDING, ARE ASSOCIATED WITH HIGH SHORT-TERM MORTALITY IN PATIENTS WITH ATRIAL FIBRILLATION TREATED WITH ORAL ANTICOAGULATION
Authors: Ajar Kochar, Daniel Wojdyla, Laine Thomas, John Alexander, Sunil Rao, Claes Held, Marco Alings, Elaine Hylek, Christopher B. Granger, Jack Ansell, Lars Wallentin, Renato Lopes
Journal: Journal of the American College of Cardiology (2019)
Extragenital chlamydia infection among active-duty women in the United States Navy
Authors: Robert Deiss, Morgan Byrne, Sara M. Echols, Stephanie M. Cammarata, Lynda Potswald, Eduardo Gomez, Jennifer A. Curry, Eric Garges, Grace Macalino, Brian K. Agan, Mary F. Bavaro
Journal: Military Medical Research (2019)

Pharyngeal and anorectal reservoirs of gonorrhea (GC) and chlamydia (CT) are increasingly recognized among heterosexual women. While a number of studies performed at sexually transmitted disease (STD) clinics have found a high prevalence of extragenital GC/CT infection, such screening is typically not offered during routine primary care visits for women. We sought to define the prevalence of and factors associated with extragenital GC/CT among women in the U.S. Navy. We recruited servicewomen stationed in San Diego, California, between the ages of 18 and 25 who presented for an annual physical exam between January and September, 2017. Nucleic acid amplification testing was performed on swabs collected at endocervical, oropharyngeal and anorectal sites to assess the presence of GC/CT. An anonymous behavioral questionnaire was also administered to characterize sexual risk. Descriptive statistics were used to compare women with and without a prior history of any sexually transmitted infection (STI) (self-report) along with a current GC/CT diagnosis. This study was approved by the Institutional Review Board of the Uniformed Services University of Health Sciences. Of the 75 patients who were approached, 60 subjects were enrolled in the study, including white 20 (33.3%), black/African American 18 (31.0%), Hispanic/Latina 13 (21.7%) and Asian/Pacific Islander 9 (15.5%) women. Among all the women, six (10.0%) were diagnosed with CT infection, all via endocervical exam. Of these, five (8.3%) had concurrent anorectal infection, including two cases (3.3%) accompanied by pharyngeal infection. Of the subjects, 15 (25.0%) reported anal intercourse in their most recent sexual encounter, most of which was condomless (13/15, 86.7%). A high number of women who reported sex with a casual male partner (19/45, 42.2%) reported rarely or never using condoms; last, 41.7% consuming at least 3 drinks on a typical drinking day, and one-third of the reported drinking more than once per week. We found a high prevalence of anorectal CT infection, although no infections were detected without concurrent endocervical involvement. Nonetheless, the high prevalence of condomless anal intercourse reported by participants argues for further study and ongoing consideration of extragenital screening among high-risk patients. Behavioral interventions are also warranted given the high prevalence of sexual and related risk factors.
Abstract 273: Autophagy Impairment is Associated With Defects in Mitochondrial Bioenergetics in Doxorubicin Cardiomyopathy
Authors: Chowdhury S Abdullah, Shafiul Alam, Richa Aishwarya, Sumitra Miriyala, Manikandan Panchatcharam, Christopher B Pattillo, Anthony W Orr, Junichi Sadoshima, Joseph A Hill, Md. Shenuarin Bhuiyan
Journal: Circulation Research (2018)

Introduction: Doxorubicin (Dox) associated cardiotoxicity limits its use in clinical practice. Despite extensive studies it is still unclear if Dox-induces autophagy activation or inhibition. Also a role for autophagy dysregulation contributing to mitochondrial dysfunction in Dox-cardiotoxicity is unknown. Hypothesis: Dox-mediated impairment of the autophagy degradation process contributes to mitochondrial dysfunction during the development of cardiomyopathy. Methods and results: Time course study of acute Dox treatment (20mg/kg, i.p.) showed accumulation of LC3-II in heart lysates at day five. We also confirmed Dox-induced autophagosome accumulation in vivo by using GFP-LC3 and mRFP-GFP-LC3 transgenic (Tg) mice. The autophagy flux assay confirmed that Dox-induced accumulation of autophagosome is due to blockade of the lysosomal degradation process. Mitochondria isolated from acute Dox-treated hearts (at day 5) showed significant suppression of the oxygen consumption rate (OCR). Chronic Dox-cardiotoxicity induced by four weekly consecutive i.p. Injections of Dox (5 mg/kg each) also exhibited time-dependent accumulation of LC3 puncta in GFP-LC3 Tg hearts. LC3-II levels in both whole cell and mitochondrial fraction were increased in Dox-treated hearts. The mitochondria in chronic dox-treated hearts (12 weeks) also showed significant suppression of OCR. To test whether autophagy induction/activation can rescue mitochondrial dysfunction in Dox-cardiotoxicity, we subjected cardiac specific αMHC-Atg7 Tg mice to acute Dox treatment. Mitochondria from Dox-treated αMHC-Atg7 Tg mice (at day 5) exhibited significant preservation of mitochondrial respiratory parameters including basal, ATP linked and maximal respiration. Conclusions: Our study confirmed that both acute and chronic Dox-cardiotoxicity is associated with inhibition of the autophagic degradation process associated with suppression of mitochondrial respiration. Notably, autophagy activation/induction preserves mitochondrial function in Dox-treated hearts, underscoring the importance of autophagy in maintaining physiologically normal mitochondrial respiration in hearts under genotoxic stress.
COMBINATION OF INVASIVE ANGIOGRAPHY AND CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY AS A NOVEL IMAGING FUSION MODALITY TO IMPROVE ANTEGRADE REVASCULARIZATION OF CORONARY CHRONIC TOTAL OCCLUSION
Authors: Apurva Patel, Ponraj Chinnadurai, Su Min Chang, Neal Kleiman, Alpesh Shah
Journal: Journal of the American College of Cardiology (2019)
MYOCARDIAL BLOOD FLOW AND TRACER WASHOUT RATE IN 13N-AMMONIA POSITRON EMISSION TOMOGRAPHY IMAGING PREDICT VIABILITY IN ISCHEMIC CARDIOMYOPATHY
Authors: Dominik C. Benz, Paola Ferro, Nico A. Safa, Moritz Schwyzer, Dimitri Patriki, Elia von Felten, Christel H. Kamani, Andreas Giannopoulos, Christoph Gräni, Catherine Gebhard, Aju Paul Pazhenkottil, Philipp A. Kaufmann, Ronny Buechel
Journal: Journal of the American College of Cardiology (2019)
A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases
Authors: Roshan S Prabhu, Brandon E Turner, Anthony L Asher, Samuel R Marcrom, John B Fiveash, Paul M Foreman, Robert H Press, Kirtesh R Patel, Walter J Curran, William G Breen, Paul D Brown, Krishan R Jethwa, Inga S Grills, Jessica D Arden, Lauren M Foster, Matthew A Manning, Joseph D Stern, Scott G Soltys, Stuart H Burri
Journal: Neuro-Oncology (2019)

Abstract Background Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known. Methods Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical (“sugarcoating,” cLMD). Results The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, P = 0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal radiotherapy (RT) (10%), and other (16%), with 58% receiving a WBRT-containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs 68%, P = 0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs 3.3 mo, P &lt; 0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs classical) was significant, but type of salvage RT (WBRT vs focal) was not. Conclusions Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical “sugarcoating” LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT.
OPTIMIZATION OF LIPID-LOWERING TREATMENT BEFORE DISCHARGE AFTER ACUTE MYOCARDIAL INFARCTION: THE ROUTINE APPLICATION OF A FRENCH CONSENSUS
Authors: Buonvino Camille, Jean Ferrières, Michel Farnier, Eric Bruckert, Michel Krempf, Celine Tchaoussoff, Francois Schiele
Journal: Journal of the American College of Cardiology (2019)