Effect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: A randomized, double-blind, placebo-controlled study

AbstractObjectives. This study examined the of metoprolol on left ventricular performance, efficiency, neurohormonal activation and myocardial respiratory quotient in patients with dilated cardiomyopathy.Background.The mechanism by which beta-adrenergie blockade improves ejection fraction in patients with dilated cardiomyopathy remains an enigma. Thus, we undertook an extensive hemodynamic evaluation of this mechanism. In addition, because animal models have shown that catecholamine exposure may increase relative fatty acid utilization, we hypothesized that antagonism of sympathetic stimulation may result in increased carbohydrate utilization.Methods. This was a randomized, double-blind, prospective trial in which 24 men with nonischemic dilated cardiomyopathy underwent cardiac catheterization before and after 3 months of therapy with metoprolol (n = 15) or placebo (n = 9) in addition to standard therapy. Pressure-volume relations were examined using a micromanometer catheter and digital ventriculography.Results. At baseline, the placebo-treated patients had somewhat more advanced left ventricular dysfunction. Ejection fraction and left ventricular performance improved only in the metoprolol-treated patients. Stroke and minute work increased without an increase in myocardial oxgen consumption, suggesting increased myocardial efficiency. Further increases in ejection fraction were seen between 3 and 6 months in the metoprolol group. The placebo group had a significant increase in ejection fraction only after crossover to metoprolol. A significant relation the change in coronary sinus norepinephrine and myocardial respiratory quotient was seen, suggesting a possible effect of adrenergic deactivation on substrate utilization.Conclusions. These data demonstrate that in patients with cardiomyopthy, metoprolol treatment improves myocardial performance and energetics, and favorably alters substrate utilization. Beta-adrenergic blocking agents, such as metoprolol, are hemodynamically and energetically beneficial in the treatment of myocardial failure

From Interactions to Institutions: Microprocesses of Framing and Mechanisms for the Structuring of Institutional Fields

Despite the centrality of meaning to institutionalization, little attention has been paid to how meanings evolve and amplify to become institutionalized cultural conventions. We develop an interactional framing perspective to explain the microprocesses and mechanisms by which this occurs. We identify three amplification processes and three ways frames stack up or laminate that become the building blocks for diffusion and institutionalization of meanings within organizations and fields. Although we focus on “bottom-up” dynamics, we argue that framing occurs in a politicized social context and is inherently bidirectional, in line with structuration, because microlevel interactions instantiate macrostructures. We consider how our approach complements other theories of meaning making, its utility for informing related theoretical streams, and its implications for organizing at the meso and macro levels

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Suspended sediment characterization and tracing using a magnetic fingerprinting technique : Bassenthwaite Lake, Cumbria, UK.

Robust identification of catchment suspended sediment sources is a prerequisite both for understanding sediment delivery processes and targeting of effective mitigation measures. Fine sediment delivery can pose universal management problems, especially with regard to nutrient run-off and lake siltation. Here, 19 suspended sediment samplers were located within the three main tributary inflows to Lake Bassenthwaite, a key but vulnerable site of special scientific interest, with water quality problems linked to accelerated delivery of fine sediment. Magnetic properties of contemporary suspended sediments, collected on a monthly basis, were measured on a particle size-specific basis and compared with the lake sediment core-tops. Ferrimagnetic grain size and magnetic ‘hardness’ vary significantly between the suspended sediments collected from the different tributaries, with the 8–31 μm and 31–63 μm clastic grain fractions displaying greatest magnetic contrasts. Postdepositional formation of bacterial magnetosomes is evident in the 2–8 μm and < 2 μm fractions of the lake sediments. Thus, for comparison with the potential source suspended sediments, we use only the detrital, clastic fractions, 8–31 μm and 31–63 μm. The lake sediment magnetic properties show little spatial variation, indicating through-lake transport of sediment (no evidence was found of postdepositional diagenetic sulphide formation). Magnetic comparisons between the potential sources and the lake surface sediments indicate that Newlands Beck, providing only ~ 10% of the lake’s hydraulic load, is the main contributor of sediment to the deep basin of the lake. Sediments from the River Derwent subcatchment, contributing ~ 80% of the hydraulic load, are possibly stored either on the floodplain or in shallower areas of the lake

Holocene sediment dynamics in an upland temperate lake catchment : climatic and land-use impacts.

Accelerated erosion and transport of fine sediment from upland temperate catchments can reflect increased erosivity and/or erodibility, due in turn to climatic and/or human forcing. Identification of sediment fluxes and sources over Holocene timescales can both enable understanding of the relative impacts of these forcings, and provide perspective on recent sediment fluxes. Here we present a ~ 5,500 year record of sediment fluxes and sources from Lake Bassenthwaite utilising magnetic measurements and fuzzy clustering, coupled with independent pollen and archaeological records, to identify the timing and impact of catchment disturbance. This record shows that recent sediment flux increases (i.e., within the last 150 years) are unprecedented in scale throughout the mid-late Holocene and appear to be in response to specific human changes occurring within the catchment. Earlier episodes of human activity, from the mid-Holocene onwards, show no link with increased lake sediment fluxes, indicating either limited catchment impact and/or ‘buffering’ through within-catchment sediment storage. Increasingly intensive land use and reduction of sediment storage through revetment construction on a key inflow, Newlands Beck, have resulted in 3 x increases in lake sediment flux. These data may be significant for other upland temperate areas, as increasing land use pressures and reduced sediment storage capacity may not only increase contemporary sediment flux, but increase sensitivity to predicted increases in rainfall and storminess as a result of global warming

Surgeon-Specific Reports in General Surgery: Establishing Benchmarks for Peer Comparison Within a Single Hospital

© 2016 American College of Surgeons. Background Methods to assess a surgeon\u27s individual performance based on clinically meaningful outcomes have not been fully developed, due to small numbers of adverse outcomes and wide variation in case volumes. The Achievable Benchmark of Care (ABC) method addresses these issues by identifying benchmark-setting surgeons with high levels of performance and greater case volumes. This method was used to help surgeons compare their surgical practice to that of their peers by using merged National Surgical Quality Improvement Program (NSQIP) and Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) data to generate surgeon-specific reports. Study design A retrospective cohort study at a single institution\u27s department of surgery was conducted involving 107 surgeons (8,660 cases) over 5.5 years. Stratification of more than 32,000 CPT codes into 16 CPT clusters served as the risk adjustment. Thirty-day outcomes of interest included surgical site infection (SSI), acute kidney injury (AKI), and mortality. Performance characteristics of the ABC method were explored by examining how many surgeons were identified as benchmark-setters in view of volume and outcome rates within CPT clusters. Results For the data captured, most surgeons performed cases spanning a median of 5 CPT clusters (range 1 to 15 clusters), with a median of 26 cases (range 1 to 776 cases) and a median of 2.8 years (range 0 to 5.5 years). The highest volume surgeon for that CPT cluster set the benchmark for 6 of 16 CPT clusters for SSIs, 8 of 16 CPT clusters for AKIs, and 9 of 16 CPT clusters for mortality. Conclusions The ABC method appears to be a sound and useful approach to identifying benchmark-setting surgeons within a single institution. Such surgeons may be able to help their peers improve their performance

Surgeon-Specific Reports in General Surgery:Establishing Benchmarks for Peer Comparison Within a Single Hospital

© 2016 American College of Surgeons. Background Methods to assess a surgeon\u27s individual performance based on clinically meaningful outcomes have not been fully developed, due to small numbers of adverse outcomes and wide variation in case volumes. The Achievable Benchmark of Care (ABC) method addresses these issues by identifying benchmark-setting surgeons with high levels of performance and greater case volumes. This method was used to help surgeons compare their surgical practice to that of their peers by using merged National Surgical Quality Improvement Program (NSQIP) and Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) data to generate surgeon-specific reports. Study design A retrospective cohort study at a single institution\u27s department of surgery was conducted involving 107 surgeons (8,660 cases) over 5.5 years. Stratification of more than 32,000 CPT codes into 16 CPT clusters served as the risk adjustment. Thirty-day outcomes of interest included surgical site infection (SSI), acute kidney injury (AKI), and mortality. Performance characteristics of the ABC method were explored by examining how many surgeons were identified as benchmark-setters in view of volume and outcome rates within CPT clusters. Results For the data captured, most surgeons performed cases spanning a median of 5 CPT clusters (range 1 to 15 clusters), with a median of 26 cases (range 1 to 776 cases) and a median of 2.8 years (range 0 to 5.5 years). The highest volume surgeon for that CPT cluster set the benchmark for 6 of 16 CPT clusters for SSIs, 8 of 16 CPT clusters for AKIs, and 9 of 16 CPT clusters for mortality. Conclusions The ABC method appears to be a sound and useful approach to identifying benchmark-setting surgeons within a single institution. Such surgeons may be able to help their peers improve their performance