Abstract Background Wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly recognized as an important cause of heart failure. Objectives The purpose of this study was to determine the ...natural history of ATTRwt and the predictors of survival. Methods We retrospectively reviewed patients diagnosed with ATTRwt at the Mayo Clinic through 2013 and recorded clinical data and survival data. Factors affecting overall survival (OS) were identified, and a prognostic staging system was developed. Results The median age of the 360 patients diagnosed before death was 75 years (range: 47 to 94 years), and 91% were male. Presenting signs and symptoms included dyspnea or heart failure in 67% and atrial arrhythmias in 62%. Median OS from diagnosis was 3.6 years and did not change over time. Multivariate predictors of mortality included age, ejection fraction, pericardial effusion, N-terminal pro–B-type natriuretic peptide, and troponin T. A staging system was developed that used thresholds of troponin T (0.05 ng/ml) and N-terminal pro–B-type natriuretic peptide (3,000 pg/ml). The respective 4-year OS estimates were 57%, 42%, and 18% for stage I (both values below cutoff), stage II (one above), and stage III (both above), respectively. Stage III patients were at an increased risk of mortality after adjustment for age and sex compared with stage I patients (hazard ratio: 3.6; p < 0.001). Conclusions The natural history of ATTRwt is poor. We report a novel cardiac biomarker staging system that enables risk stratification in an era of emerging treatment strategies.
Asymptomatic left ventricular dysfunction (ALVD) is present in 3-6% of the general population, is associated with reduced quality of life and longevity, and is treatable when found
. An inexpensive, ...noninvasive screening tool for ALVD in the doctor's office is not available. We tested the hypothesis that application of artificial intelligence (AI) to the electrocardiogram (ECG), a routine method of measuring the heart's electrical activity, could identify ALVD. Using paired 12-lead ECG and echocardiogram data, including the left ventricular ejection fraction (a measure of contractile function), from 44,959 patients at the Mayo Clinic, we trained a convolutional neural network to identify patients with ventricular dysfunction, defined as ejection fraction ≤35%, using the ECG data alone. When tested on an independent set of 52,870 patients, the network model yielded values for the area under the curve, sensitivity, specificity, and accuracy of 0.93, 86.3%, 85.7%, and 85.7%, respectively. In patients without ventricular dysfunction, those with a positive AI screen were at 4 times the risk (hazard ratio, 4.1; 95% confidence interval, 3.3 to 5.0) of developing future ventricular dysfunction compared with those with a negative screen. Application of AI to the ECG-a ubiquitous, low-cost test-permits the ECG to serve as a powerful screening tool in asymptomatic individuals to identify ALVD.
For decades, human brucellosis has been recognized worldwide as a significant cause of morbidity, yet the annual incidence of this disease remains unknown. We analyzed this frequency, using ...international reports (2005-2019), identifying information gaps, and distinguishing a possible path forward.
A novel approach to estimating the incidence of this disease was explored. We utilized annual health data extracted from the World Organization for Animal Health (OIE)-World Animal Health Information System (WAHIS) database, assessing the dataset completeness and representativeness of the data for the world population. Additionally, we assessed the reported country level human brucellosis case counts and the factors that influenced the observed changes over time. Our analysis revealed incomplete and unrepresentative information, preventing the estimation of annual human brucellosis case incidence at the global level. In the OIE-WAHIS database, only 48.4% of the required reports have been submitted as of 2019, with approximately 47.3% of the world population represented. Additionally, geographic regions were disproportionate in completeness, representativeness, and actual reported case counts. Africa and Asia constituted the majority of reported cases, while simultaneously submitting the lowest percentage of reports as well as covering the lowest percentage of their populations within those reports, when compared to the rest of the world.
The global annual frequency of human brucellosis cases remains elusive. Furthermore, there exists great heterogeneity in diagnostic, surveillance, and reporting systems worldwide, calling into question the validity of available information. This study reveals that the Neglected Zoonotic Disease priority status for brucellosis should be restored.
Continual efferocytic clearance of apoptotic cells (ACs) by macrophages prevents necrosis and promotes injury resolution. How continual efferocytosis is promoted is not clear. Here, we show that the ...process is optimized by linking the metabolism of engulfed cargo from initial efferocytic events to subsequent rounds. We found that continual efferocytosis is enhanced by the metabolism of AC-derived arginine and ornithine to putrescine by macrophage arginase 1 (Arg1) and ornithine decarboxylase (ODC). Putrescine augments HuR-mediated stabilization of the mRNA encoding the GTP-exchange factor Dbl, which activates actin-regulating Rac1 to facilitate subsequent rounds of AC internalization. Inhibition of any step along this pathway after first-AC uptake suppresses second-AC internalization, whereas putrescine addition rescues this defect. Mice lacking myeloid Arg1 or ODC have defects in efferocytosis in vivo and in atherosclerosis regression, while treatment with putrescine promotes atherosclerosis resolution. Thus, macrophage metabolism of AC-derived metabolites allows for optimal continual efferocytosis and resolution of injury.
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•Macrophages take up arginine and ornithine from apoptotic cells during efferocytosis•Arg1 and ODC convert apoptotic cell-derived arginine and ornithine into putrescine•Putrescine augments subsequent rounds of efferocytosis by increasing Rac1 activation•Lack of Arg1 or ODC blunts continual efferocytosis and resolution of atherosclerosis
Macrophages engulf apoptotic cells (ACs) by continual efferocytosis to prevent inflammation and necrosis. Here, Yurdagul et. al. show that this process is linked to the metabolism of AC-derived arginine or ornithine to putrescine, which is required for the optimization of subsequent rounds of efferocytosis and proper resolution of atherosclerosis.
Purpose To examine the effects of subconcussive impacts resulting from a single season of youth (age range, 8-13 years) football on changes in specific white matter (WM) tracts as detected with ...diffusion-tensor imaging in the absence of clinically diagnosed concussions. Materials and Methods Head impact data were recorded by using the Head Impact Telemetry system and quantified as the combined-probability risk-weighted cumulative exposure (RWE
). Twenty-five male participants were evaluated for seasonal fractional anisotropy (FA) changes in specific WM tracts: the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus, and superior longitudinal fasciculus (SLF). Fiber tracts were segmented into a central core and two fiber terminals. The relationship between seasonal FA change in the whole fiber, central core, and the fiber terminals with RWE
was also investigated. Linear regression analysis was conducted to determine the association between RWE
and change in fiber tract FA during the season. Results There were statistically significant linear relationships between RWE
and decreased FA in the whole (R
= 0.433; P = .003), core (R
= 0.3649; P = .007), and terminals (R
= 0.5666; P < .001) of left IFOF. A trend toward statistical significance (P = .08) in right SLF was observed. A statistically significant correlation between decrease in FA of the right SLF terminal and RWE
was also observed (R
= 0.2893; P = .028). Conclusion This study found a statistically significant relationship between head impact exposure and change of FA fractional anisotropy value of whole, core, and terminals of left IFOF and right SLF's terminals where WM and gray matter intersect, in the absence of a clinically diagnosed concussion.
RSNA, 2016.
Sex and age have long been known to affect the ECG. Several biologic variables and anatomic factors may contribute to sex and age-related differences on the ECG. We hypothesized that a convolutional ...neural network (CNN) could be trained through a process called deep learning to predict a person's age and self-reported sex using only 12-lead ECG signals. We further hypothesized that discrepancies between CNN-predicted age and chronological age may serve as a physiological measure of health.
We trained CNNs using 10-second samples of 12-lead ECG signals from 499 727 patients to predict sex and age. The networks were tested on a separate cohort of 275 056 patients. Subsequently, 100 randomly selected patients with multiple ECGs over the course of decades were identified to assess within-individual accuracy of CNN age estimation.
Of 275 056 patients tested, 52% were males and mean age was 58.6±16.2 years. For sex classification, the model obtained 90.4% classification accuracy with an area under the curve of 0.97 in the independent test data. Age was estimated as a continuous variable with an average error of 6.9±5.6 years (R-squared =0.7). Among 100 patients with multiple ECGs over the course of at least 2 decades of life, most patients (51%) had an average error between real age and CNN-predicted age of <7 years. Major factors seen among patients with a CNN-predicted age that exceeded chronologic age by >7 years included: low ejection fraction, hypertension, and coronary disease (P<0.01). In the 27% of patients where correlation was >0.8 between CNN-predicted and chronologic age, no incident events occurred over follow-up (33±12 years).
Applying artificial intelligence to the ECG allows prediction of patient sex and estimation of age. The ability of an artificial intelligence algorithm to determine physiological age, with further validation, may serve as a measure of overall health.
Global Estimate of Human Brucellosis Incidence Laine, Christopher G; Johnson, Valen E; Scott, H. Morgan ...
Emerging infectious diseases,
09/2023, Letnik:
29, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Brucellosis is a major public health concern worldwide, especially for persons living in resource-limited settings. Historically, an evidence-based estimate of the global annual incidence of human ...cases has been elusive. We used international public health data to fill this information gap through application of risk metrics to worldwide and regional at-risk populations. We performed estimations using 3 statistical models (weighted average interpolation, bootstrap resampling, and Bayesian inference) and considered missing information. An evidence-based conservative estimate of the annual global incidence is 2.1 million, significantly higher than was previously assumed. Our models indicate Africa and Asia sustain most of the global risk and cases, although areas within the Americas and Europe remain of concern. This study reveals that disease risk and incidence are higher than previously suggested and lie mainly within resource-limited settings. Clarification of both misdiagnosis and underdiagnosis is required because those factors will amplify case estimates.
Few data exist on the contemporary profiles and outcomes of patients with significant aortic regurgitation (AR).
This study sought to assess the benefits of aortic valve repair or replacement (AVR) ...and the prognostic value of left ventricular (LV) dimensions in significant AR.
From 2006 to 2017, consecutive patients with ≥moderate-severe chronic AR without prior heart surgery, myocardial infarction, or overt coronary artery disease were included.
Of 748 participants (58 ± 17 years of age; 82% men), 387 (52%) were medically treated, and 361 (48%) had AVR. Of 361 patients having AVR, 334 (93%) met guideline criteria: Class I indications in 284 (79%) patients, which included symptoms in 236, and Class II indications in 50 (14%). The remaining 27 (7%) opted for surgery without Class I or II indications. At a median follow-up of 4.9 years (interquartile range: 2.3 to 8.3 years), 125 (17%) patients had died. Age, comorbidities, baseline symptoms, and higher LV end-systolic dimension index (LVESDi) were associated with all-cause mortality (all p ≤ 0.01). Compared with patients having LVESDi <20 mm/m2, those with LVESDi 20 to 25 mm/m2 (hazard ratio: 1.53; 95% confidence interval: 1.01 to 2.31) and ≥25 mm/m2 (HR: 2.23; 95% confidence interval: 1.32 to 3.77) had increased risks of death. AVR was associated with better survival (p < 0.0001). Patients with Class I indications for surgery had inferior post-operative survival (p < 0.003).
Class I indications for surgery, mainly symptoms, are the most common triggers for AVR. Class II indications were associated with better post-operative outcome and thus merit more attention. LVESDi was the only LV parameter independently associated with all-cause mortality and the ideal cutoff seems to be lower than previously recommended.
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Abstract Humans exhibit a remarkable capacity for flexible thought and action. Despite changing internal needs and external context, individuals maintain stable goals and pursue purposeful action. ...Functional neuroimaging research examining the neural underpinnings of such behavioral flexibility has progressed within several distinct traditions, as evident in the largely separate literatures on “cognitive control” and on “decision making.” Both topics investigate the formulation of desires and intentions, the integration of knowledge and context, and the resolution of conflict and uncertainty. Additionally, each recognizes the fundamental role of the prefrontal cortex in supporting flexible selection of behavior. But despite this notable overlap, neuroimaging studies in cognitive control and decision making have exerted only limited influence on each other, in part due to differences in their theoretical and experimental groundings. Additionally, the precise organization of control processing within prefrontal cortex has remained unclear, fostering an acceptance of vague descriptions of decision making in terms of canonical cognitive control functions such as “inhibition” or “self-control.” We suggest a unifying role for models of the hierarchical organization of action selection within prefrontal cortex. These models provide an important conceptual link between decision-making phenomena and cognitive-control processes, potentially facilitating cross-fertilization between these topics.
We present preliminary trigonometric parallaxes of 184 late-T and Y dwarfs using observations from Spitzer (143), the U.S. Naval Observatory (18), the New Technology Telescope (14), and the United ...Kingdom Infrared Telescope (9). To complete the 20 pc census of ≥T6 dwarfs, we combine these measurements with previously published trigonometric parallaxes for an additional 44 objects and spectrophotometric distance estimates for another 7. For these 235 objects, we estimate temperatures, sift into five 150 K wide Teff bins covering the range 300-1050 K, determine the completeness limit for each, and compute space densities. To anchor the high-mass end of the brown dwarf mass spectrum, we compile a list of early- to mid-L dwarfs within 20 pc. We run simulations using various functional forms of the mass function passed through two different sets of evolutionary code to compute predicted distributions in Teff. The best fit of these predictions to our L, T, and Y observations is a simple power-law model with 0.6 (where ), meaning that the slope of the field substellar mass function is in rough agreement with that found for brown dwarfs in nearby star-forming regions and young clusters. Furthermore, we find that published versions of the log-normal form do not predict the steady rise seen in the space densities from 1050 to 350 K. We also find that the low-mass cutoff to formation, if one exists, is lower than ∼5 MJup, which corroborates findings in young, nearby moving groups and implies that extremely low-mass objects have been forming over the lifetime of the Milky Way.
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