Advanced medical interventions in pleural disease

The burden of a number of pleural diseases continues to increase internationally. Although many pleural procedures have historically been the domain of interventional radiologists or thoracic surgeons, in recent years, there has been a marked expansion in the techniques available to the pulmonologist. This has been due in part to both technological advancements and a greater recognition that pleural disease is an important subspecialty of respiratory medicine. This article summarises the important literature relating to a number of advanced pleural interventions, including medical thoracoscopy, the insertion and use of indwelling pleural catheters, pleural manometry, point-of-care thoracic ultrasound, and image-guided closed pleural biopsy. We also aim to inform the reader regarding the latest updates to more established procedures such as chemical pleurodesis, thoracentesis and the management of chest drains, drawing on contemporary data from recent randomised trials. Finally, we shall look to explore the challenges faced by those practicing pleural medicine, especially relating to training, as well as possible future directions for the use and expansion of advanced medical interventions in pleural disease

The right ventricular response to lung resection

Objectives: Lung cancer is a leading cause of cancer death and in suitable cases the best chance of cure is offered by surgery. Lung resection is associated with significant postoperative cardiorespiratory morbidity, with dyspnea and reduced functional capacity as dominant features. These changes are poorly associated with deterioration in pulmonary function and a potential role of right ventricular (RV) dysfunction has been hypothesized. Cardiovascular magnetic resonance imaging is a reference method for noninvasive assessment of RV function and has not previously been applied to this population. Methods: We used cardiovascular magnetic resonance imaging to assess the RV response to lung resection. Cardiovascular magnetic resonance imaging with volume and flow analysis was performed on 27 patients preoperatively, on postoperative day 2 and at 2 months. Left ventricular ejection fraction and RV ejection fraction, the ratio of stroke volume to end systolic volume, pulmonary artery acceleration time, and distensibility of main and branch pulmonary arteries were studied. Results: Mean ± standard deviation RV ejection fraction deteriorated from 50.5% ± 6.9% preoperatively to 45.6% ± 4.5% on postoperative day 2 and remained depressed at 44.9% ± 7.7% by 2 months (P = .003). The ratio of stroke volume to end systolic volume deteriorated from median 1.0 (quartile 1, quartile 3, 0.9, 1.2) preoperatively to median 0.8 (quartile 1, quartile 3, 0.7, 1.0) on postoperative day 2 (P = .011). On postoperative day 2 there was a decrease in pulmonary artery acceleration time and operative pulmonary artery distensibility (P < .030 for both). There were no changes in left ventricular ejection fraction during the study period (P = .621). Conclusions: These findings suggest RV dysfunction occurs following lung resection and persists 2 months after surgery. The deterioration in the ratio of stroke volume to end systolic volume suggests a mismatch between afterload and contractility. There is an increase in indices of pulsatile afterload resulting from the operative pulmonary artery

Percutaneous coronary intervention versus medical therapy in patients with angina and grey-zone fractional flow reserve values: a randomised clinical trial

Introduction: There is conflicting evidence regarding the benefits of percutaneous coronary intervention (PCI) in patients with grey zone fractional flow reserve (GZFFR artery) values (0.75–0.80). The prevalence of ischaemia is unknown. We wished to define the prevalence of ischaemia in GZFFR artery and assess whether PCI is superior to optimal medical therapy (OMT) for angina control. Methods: We enrolled 104 patients with angina with 1:1 randomisation to PCI or OMT. The artery was interrogated with a Doppler flow/pressure wire. Patients underwent Magnetic Resonance Imaging (MRI) with follow-up at 3 and 12 months. The primary outcome was angina status at 3 months using the Seattle Angina Questionnaire (SAQ). Results: 104 patients (age 60±9 years), 79 (76%) males and 79 (76%) Left Anterior Descending (LAD) stenoses were randomised. Coronary physiology and SAQ were similar. Of 98 patients with stress perfusion MRI data, 17 (17%) had abnormal perfusion (≥2 segments with ≥25% ischaemia or ≥1 segment with ≥50% ischaemia) in the target GZFFR artery. Of 89 patients with invasive physiology data, 26 (28%) had coronary flow velocity reserve <2.0 in the target GZFFR artery. After 3 months of follow-up, compared with patients treated with OMT only, patients treated by PCI and OMT had greater improvements in SAQ angina frequency (21 (28) vs 10 (23); p=0.026) and quality of life (24 (26) vs 11 (24); p=0.008) though these differences were no longer significant at 12 months. Conclusions: Non-invasive evidence of major ischaemia is uncommon in patients with GZFFR artery. Compared with OMT alone, patients randomised to undergo PCI reported improved symptoms after 3 months but these differences were no longer significant after 12 months

NICER X-ray Observations of Eta Carinae During its Most Recent Periastron Passage

We report high-precision X-ray monitoring observations in the 0.4-10 keV band of the luminous, long-period colliding-wind binary Eta Carinae up to and through its most recent X-ray minimum/periastron passage in February 2020. Eta Carinae reached its observed maximum X-ray flux on 7 January 2020, at a flux level of $3.30 \times 10^{-10}$ ergs s$^{-1}$ cm$^{-2}$, followed by a rapid plunge to its observed minimum flux, $0.03 \times 10^{-10}$ ergs s$^{-1}$ cm$^{-2}$ near 17 February 2020. The NICER observations show an X-ray recovery from minimum of only $\sim$16 days, the shortest X-ray minimum observed so far. We provide new constraints of the "deep" and "shallow" minimum intervals. Variations in the characteristic X-ray temperature of the hottest observed X-ray emission indicate that the apex of the wind-wind "bow shock" enters the companion's wind acceleration zone about 81 days before the start of the X-ray minimum. There is a step-like increase in column density just before the X-ray minimum, probably associated with the presence of dense clumps near the shock apex. During recovery and after, the column density shows a smooth decline, which agrees with previous $N_{H}$ measurements made by SWIFT at the same orbital phase, indicating that changes in mass-loss rate are only a few percent over the two cycles. Finally, we use the variations in the X-ray flux of the outer ejecta seen by NICER to derive a kinetic X-ray luminosity of the ejecta of $\sim 10^{41}$ ergs s$^{-1}$ near the time of the "Great Eruption'

High Energy Astrophysics Program (HEAP)

This report reviews activities performed by the members of the USRA contract team during the 6 months of the reporting period and projected activities during the coming 6 months. Activities take place at the Goddard Space Flight Center, within the Laboratory for High Energy Astrophysics. Developments concern instrumentation, observation, data analysis, and theoretical work in astrophysics. Supported missions include advanced Satellite for Cosmology and Astrophysics (ASCA), X-Ray Timing Experiment (XTE), X-Ray Spectrometer (XRS), Astro-E, High Energy Astrophysics Science Archive Research Center (HEASARC) and others

Eta Carinae: an evolving view of the central binary, its interacting winds and its foreground ejecta

FUV spectra of Eta Car, recorded across two decades with HST/STIS, document multiple changes in resonant lines caused by dissipating extinction in our line of sight. The FUV flux has increased nearly ten-fold which has led to increased ionization of the multiple shells within the Homunculus and photo-destruction of molecular hydrogen. Comparison of observed resonant line profiles with CMFGEN model profiles allows separation of wind-wind collision and shell absorptions from the primary wind, P Cygni profiles.The dissipating occulter preferentially obscured the central binary and interacting winds relative to the very extended primary wind. We are now able to monitor changes in the colliding winds with orbital phase. High velocity transient absorptions occurred across the most recent periastron passage, indicating acceleration of the primary wind by the secondary wind which leads to a downstream, high velocity bowshock that is newly generated every orbital period. There is no evidence of changes in the properties of the binary winds.Comment: 36 pages, 22 figures, accepted Astrophysical Journa

Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription

AbstractBackground: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3.Results: SB-216763 and SB-415286 are structurally distinct maleimides that inhibit GSK-3α in vitro, with Kis of 9 nM and 31 nM respectively, in an ATP competitive manner. These compounds inhibited GSK-3β with similar potency. However, neither compound significantly inhibited any member of a panel of 24 other protein kinases. Furthermore, treatment of cells with either compound stimulated responses characteristic of extracellular stimuli that are known to inhibit GSK-3 activity. Thus, SB-216763 and SB-415286 stimulated glycogen synthesis in human liver cells and induced expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. In both cases, compound treatment was demonstrated to inhibit cellular GSK-3 activity as assessed by activation of glycogen synthase, which is a direct target of this kinase.Conclusions: SB-216763 and SB-415286 are novel, potent and selective cell permeable inhibitors of GSK-3. Therefore, these compounds represent valuable pharmacological tools with which the role of GSK-3 in cellular signalling can be further elucidated. Furthermore, development of similar compounds may be of use therapeutically in disease states associated with elevated GSK-3 activity such as non-insulin dependent diabetes mellitus and neurodegenerative disease

Low-dose alteplase during primary percutaneous coronary intervention according to ischemic time

Background: Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis. Objectives: This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time. Methods: This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440). Results: Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018). Conclusion: In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294