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RATIONALE: The long-acting β2-agonist/long-acting muscarinic antagonist combination indacaterol/glycopyrronium (IND/GLY) elicits bronchodilation, improves symptoms, and reduces exacerbations in COPD. Magnetic resonance imaging (MRI) of the lung with hyperpolarized gas and gadolinium contrast enhancement enables assessment of whole lung functional responses to IND/GLY. OBJECTIVES: The primary objective was assessment of effect of IND/GLY on global ventilated lung volume (%VV) versus placebo in COPD. Lung function, regional ventilation and perfusion in response to IND/GLY were also measured. METHODS: This double-blind, randomized, placebo-controlled, crossover study assessed %VV and pulmonary perfusion in patients with moderate-to-severe COPD after 8 days of once-daily IND/GLY treatment (110/50 µg) followed by 8 days of placebo, or vice versa, using inhaled hyperpolarized 3He gas and gadolinium contrast-enhanced MRI, respectively. Lung function measures including spirometry were performed for each treatment after 8 days. MEASUREMENTS AND MAIN RESULTS: Of 31 patients randomized, 29 completed both treatment periods. IND/GLY increased global %VV versus placebo (61.73% vs. 56.73%, respectively, least squares means treatment difference: 5.00% [90% CI 1.40 to 8.60]; P = 0.025). IND/GLY improved whole lung index of ventilation volume to perfusion volume (V/Q) ratio versus placebo; 94% (90% CI 83 to 105) versus 86% (90% CI 75 to 97; P = 0.047), respectively. IND/GLY showed a trend to improve diffusing capacity for carbon monoxide (DLCO) (+ 0.66 mL/min/mmHg; P = 0.082). By Day 8, forced expiratory volume in 1 s (FEV1) was increased by 0.32 L versus placebo (90% CI 0.26 to 0.38; P

Background Glagov et al. showed that no reduction in vessel lumen occurred until the atherosclerotic plaque burden exceeded 40% of the vessel area. Most major adverse cardiac events occurring in the first 4 years after a myocardial infarction arise from untreated angiographically mild, non-flow-limiting lesions at the time of the index event. We report how computed tomography (CT) coronary angiography (CCTA) can be used to non-invasively risk stratify a patient with non-obstructive coronary artery disease (CAD) and guide further management. Case summary A 69-year-old non-smoking female with hypertension, dyslipidaemia, and hypothyroidism presented with atypical chest pain. Electrocardiogram and left ventricular ejection fraction were normal. Her lipidic profile was normal. CCTA showed a lipid-rich plaque with very low attenuation (<30 HU) in the left main stem (LMS) extending into the proximal left anterior descending (LAD) and in the mid LAD artery. The maximum plaque burden in the LMS was 67% with a remodelling index of 1.375, and an area stenosis of 22%. Tissue characterization showed a lipid-rich plaque with a thin fibrous cap. The perivascular fat attenuation index (FAI) in the proximal LAD was suggestive of (−69 HU) inflamed perivascular fat. Shear stress analysis of the LMS plaque showed normal wall shear stress (WSS); however, the axial plaque stress was high. Her medications were intensified to rosuvastatin 20 mg once daily (OD) and ezetimibe 10 mg OD. The patient remained asymptomatic at 6 months follow-up. Discussion Our case exemplifies the value of CCTA as a diagnostic 'one-stop shop' (CCTA, finite element analysis, computed tomographic density [CTD], tissue characterization analysis, FAI analysis, WSS and wall strain, and etc.) when stratifying a patient with non-obstructive CAD. With further development of novel potent anti-lipidaemic and anti-inflammatory drugs, non-obstructive lesions with adverse plaque and haemodynamic parameters will have the opportunity to be treated with additional preventive pharmacological therapy. [ABSTRACT FROM AUTHOR]

The development of a multicultural center at Prospect Middle School in Pittsburgh, Pennsylvania, was a response to the increase of racism and bigotry. Academic performance for both African-American and white students has improved significantly, and overall suspension rates have dropped by nearly 50 percent. (MLF)

Background: To support translational lung MRI research with hyperpolarized 129 Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from 3 He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of 129 Xe functional metrics have not been reported.Purpose/hypothesis: To compare hyperpolarized 129 Xe and 3 He MRI-derived quantitative metrics of lung ventilation and microstructure, and their repeatability, at 1.5T.Study Type: Retrospective.Population: Fourteen healthy nonsmokers (HN), five exsmokers (ES), five patients with chronic obstructive pulmonary disease (COPD), and 16 patients with nonsmall-cell lung cancer (NSCLC).Field Strength/sequence: 1.5T. NSCLC, COPD patients and selected HN subjects underwent 3D balanced steady-state free-precession lung ventilation MRI using both 3 He and 129 Xe. Selected HN, all ES, and COPD patients underwent 2D multislice spoiled gradient-echo diffusion-weighted lung MRI using both hyperpolarized gas nuclei.Assessment: Ventilated volume percentages (VV%) and mean apparent diffusion coefficients (ADC) were derived from imaging. COPD patients performed the whole MR protocol in four separate scan sessions to assess repeatability. Same-day pulmonary function tests were performed.Statistical Tests: Intermetric correlations: Spearman's coefficient. Intergroup/internuclei differences: analysis of variance / Wilcoxon's signed rank. Repeatability: coefficient of variation (CV), intraclass correlation (ICC) coefficient.Results: A significant positive correlation between 3 He and 129 Xe VV% was observed (r = 0.860, P < 0.001). VV% was larger for 3 He than 129 Xe (P = 0.001); average bias, 8.79%. A strong correlation between mean 3 He and 129 Xe ADC was obtained (r = 0.922, P < 0.001). MR parameters exhibited good correlations with pulmonary function tests. In COPD patients, mean CV of 3 He and 129 Xe VV% was 4.08% and 13.01%, respectively, with ICC coefficients of 0.541 (P = 0.061) and 0.458 (P = 0.095). Mean 3 He and 129 Xe ADC values were highly repeatable (mean CV: 2.98%, 2.77%, respectively; ICC: 0.995, P < 0.001; 0.936, P < 0.001). DATA CONCLUSION: 129 Xe lung MRI provides near-equivalent information to 3 He for quantitative lung ventilation and microstructural MRI at 1.5T.Level Of Evidence: 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the reproducibility of indices of lung microstructure and function derived from 129Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR-derived parameters to pulse sequence design and lung inflation level. Methods Preliminary data were collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, five COPD patients were scanned on three separate days, and nine age-matched volunteers were scanned three times on one day, to assess reproducibility. Results CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level ( P < 0.001; P = 0.057, respectively). Intra-subject standard deviations of ST were lower than the previously measured differences between volunteers and subjects with interstitial lung disease. The mean coefficient of variation (CV) values of ST were 3.9 ± 1.9% and 6.0 ± 4.5% in volunteers and COPD patients, respectively, similar to CV values for whole-lung carbon monoxide diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1 ± 8.0% and 18.0 ± 19.3%, respectively. Conclusion 129Xe CSSR presents a reproducible method for estimation of alveolar septal thickness. Magn Reson Med 77:2107-2113, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. [ABSTRACT FROM AUTHOR]

Clonal hematopoiesis (CH) is more common in older persons and has been associated with an increased risk of hematological cancers and cardiovascular diseases. The most common CH mutations occur in the DNMT3A and TET2 genes and result in increased proinflammatory signaling. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (NCT01327846) evaluated the neutralizing anti-IL1β antibody canakinumab in 10,061 randomized patients with a history of myocardial infarction and persistent inflammation; DNA samples were available from 3,923 patients for targeted genomic sequencing. We examined the incidence of non-hematological malignancy by treatment assignment and CH mutations and estimated the cumulative incidence of malignancy events during trial follow-up. Patients with TET2 mutations treated with canakinumab had the lowest incidence of non-hematological malignancy across cancer types. The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab versus those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL1β blockade cooperating with CH mutations to modify the disease course. Prevention Relevance: We reveal that administering canakinumab is associated with a decrease in non-hematological malignancies among patients with clonal hematopoiesis (CH) mutations. These findings underscore canakinumab's potential in preventing cancer and provide proof of IL1β blockade collaborating with CH mutations to enhance its clinical benefits. See related Spotlight, p. 399., (©2024 American Association for Cancer Research.)

Aims: The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD)., Methods and Results: In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were randomized 1:1 to 48 h intravenous infusion of serelaxin (30 µg/kg/day) or matching placebo. The primary endpoints were change from baseline to 47 h post-initiation of the infusion in global myocardial perfusion reserve (MPR) assessed using adenosine stress perfusion cardiac magnetic resonance imaging, and applanation tonometry-derived augmentation index (AIx). Secondary endpoints were: change from baseline in AIx and pulse wave velocity, assessed at 47 h, Day 30, and Day 180; aortic distensibility at 47 h; pharmacokinetics and safety. Exploratory endpoints were the effect on cardiorenal biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), endothelin-1, and cystatin C]. Of 58 patients, 51 were included in the primary analysis (serelaxin, n = 25; placebo, n = 26). After 2 and 6 h of serelaxin infusion, mean placebo-corrected blood pressure reductions of -9.6 mmHg (P = 0.01) and -13.5 mmHg (P = 0.0003) for systolic blood pressure and -5.2 mmHg (P = 0.02) and -8.4 mmHg (P = 0.001) for diastolic blood pressure occurred. There were no between-group differences from baseline to 47 h in global MPR (-0.24 vs. -0.13, P = 0.44) or AIx (3.49% vs. 0.04%, P = 0.21) with serelaxin compared with placebo. Endothelin-1 and cystatin C levels decreased from baseline in the serelaxin group, and there were no clinically relevant changes observed with serelaxin for NT-proBNP or hsTnT. Similar numbers of serious adverse events were observed in both groups (serelaxin, n = 5; placebo, n = 7) to 180-day follow-up., Conclusion: In patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: To evaluate the reproducibility of indices of lung microstructure and function derived from 129 Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR-derived parameters to pulse sequence design and lung inflation level., Methods: Preliminary data were collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, five COPD patients were scanned on three separate days, and nine age-matched volunteers were scanned three times on one day, to assess reproducibility., Results: CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level (P < 0.001; P = 0.057, respectively). Intra-subject standard deviations of ST were lower than the previously measured differences between volunteers and subjects with interstitial lung disease. The mean coefficient of variation (CV) values of ST were 3.9 ± 1.9% and 6.0 ± 4.5% in volunteers and COPD patients, respectively, similar to CV values for whole-lung carbon monoxide diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1 ± 8.0% and 18.0 ± 19.3%, respectively., Conclusion: 129 Xe CSSR presents a reproducible method for estimation of alveolar septal thickness. Magn Reson Med 77:2107-2113, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)