Left Ventricular Structure and Function in Elite Swimmers and Runners

Sport-specific differences in the left ventricle (LV) of land-based athletes have been observed; however, comparisons to water-based athletes are sparse. The purpose of this study was to examine differences in LV structure and function in elite swimmers and runners. Sixteen elite swimmers [23 (2) years, 81% male, 69% white] and 16 age, sex, and race matched elite runners participated in the study. All athletes underwent resting echocardiography and indices of LV dimension, global LV systolic and diastolic function, and LV mechanics were determined. All results are presented as swimmers vs. runners. Early diastolic function was lower in swimmers including peak early transmitral filling velocity [76 (13) vs. 87 (11) cm ⋅ s-1, p = 0.02], mean mitral annular peak early velocity [16 (2) vs. 18 (2) cm ⋅ s-1, p = 0.01], and the ratio of peak early to late transmitral filling velocity [2.68 (0.59) vs. 3.29 (0.72), p = 0.005]. The diastolic mechanics index of time to peak untwisting rate also occurred later in diastole in swimmers [12 (10)% diastole vs. 5 (4)% diastole, p = 0.01]. Cardiac output was larger in swimmers [5.8 (1.5) vs. 4.7 (1.2) L ⋅ min-1, p = 0.04], which was attributed to their higher heart rates [56 (6) vs. 49 (6) bpm, p < 0.001] given stroke volumes were similar between groups. All other indices of LV systolic function and dimensions were similar between groups. Our findings suggest enhanced early diastolic function in elite runners relative to swimmers, which may be attributed to faster LV untwisting

Global Pyrogeography: the Current and Future Distribution of Wildfire

Climate change is expected to alter the geographic distribution of wildfire, a complex abiotic process that responds to a variety of spatial and environmental gradients. How future climate change may alter global wildfire activity, however, is still largely unknown. As a first step to quantifying potential change in global wildfire, we present a multivariate quantification of environmental drivers for the observed, current distribution of vegetation fires using statistical models of the relationship between fire activity and resources to burn, climate conditions, human influence, and lightning flash rates at a coarse spatiotemporal resolution (100 km, over one decade). We then demonstrate how these statistical models can be used to project future changes in global fire patterns, highlighting regional hotspots of change in fire probabilities under future climate conditions as simulated by a global climate model. Based on current conditions, our results illustrate how the availability of resources to burn and climate conditions conducive to combustion jointly determine why some parts of the world are fire-prone and others are fire-free. In contrast to any expectation that global warming should necessarily result in more fire, we find that regional increases in fire probabilities may be counter-balanced by decreases at other locations, due to the interplay of temperature and precipitation variables. Despite this net balance, our models predict substantial invasion and retreat of fire across large portions of the globe. These changes could have important effects on terrestrial ecosystems since alteration in fire activity may occur quite rapidly, generating ever more complex environmental challenges for species dispersing and adjusting to new climate conditions. Our findings highlight the potential for widespread impacts of climate change on wildfire, suggesting severely altered fire regimes and the need for more explicit inclusion of fire in research on global vegetation-climate change dynamics and conservation planning

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Flow-mediated dilation is acutely improved after high-intensity interval exercise

Purpose: Cardiovascular disease is characterized by decreased endothelial function. Chronic exercise training improves endothelial function in individuals with cardiovascular diseases; however, the acute endothelial responses to a single bout of exercise are not consistent in the literature. This study investigated whether a single bout of moderate-intensity endurance exercise (END) and low-volume high-intensity interval exercise (HIT) on a cycle ergometer resulted in similar acute changes in endothelial function. Methods: Ten individuals (66 ± 11 yr) with coronary artery disease (CAD) participated in two exercise sessions (END and HIT). Endothelial-dependent function was assessed using brachial artery flow-mediated dilation (FMD) preexercise and 60 min postexercise. Brachial artery diameters and velocities were determined using Doppler ultrasound before and after a 5 min ischemic period at all time points. Endothelial-independent function was assessed using a 0.4-mg sublingual dose of nitroglycerin. Results: The total work performed was higher in END (166 ± 52 kJ) compared with HIT (93 ± 28 kJ) exercise (P 0.05). Conclusions: HIT and END resulted in similar acute increases in brachial artery endothelial-dependent function in a population with dysfunction at rest, despite the difference in exercise intensities

Associations between arterial stiffness and blood pressure fluctuations after spinal cord injury

STUDY DESIGN Cross-sectional. OBJECTIVE To examine the relationship between arterial stiffness and daily fluctuations in blood pressure (BP) owing to hypotensive events and autonomic dysreflexia (AD) in individuals with a T6 and above spinal cord injury (SCI). SETTING University-based laboratory in Vancouver, BC, Canada. METHODS Twenty-six individuals (73% male; 43 (11) years) with a chronic (> 1 year post SCI), traumatic, motor-complete SCI with a neurological level of injury of C4-T6 participated in this study. Arterial stiffness was assessed using carotid-to-femoral pulse wave velocity (cfPWV). BP was measured over a 24-hr period using ambulatory BP monitoring. AD was defined as an increase in systolic BP > 20 mmHg above baseline BP. Hypotensive events were defined as a decrease in systolic BP ≥ 20 mmHg and/or diastolic BP ≥ 10 mmHg below baseline. The severity and frequency of these events were quantified and Pearson and Spearman's correlations between them and cfPWV were performed. RESULTS AD severity and frequency were not were correlated with cfPWV. For hypotensive events, both the frequency (r = 0.412, P = 0.04) and severity (Δsystolic BP; r = -0.425, P = 0.03) of these events were correlated with cfPWV. The combined total of AD and hypotensive events (9 (5) events/day) was also correlated with cfPWV (r = 0.480, P = 0.01). CONCLUSIONS Hypotensive events, and the combined frequency of both hypo- and hypertensive events within a 24-hr period are associated with increased arterial stiffness in individuals with T6 and above SCI, suggesting BP instability may play a role in arterial stiffening post SCI