The Far Ultraviolet Spectroscopic Explorer satellite observes light in the far-ultraviolet spectral region, 905-1187 Å, with a high spectral resolution. The instrument consists of four co-aligned ...prime-focus telescopes and Rowland spectrographs with microchannel plate detectors. Two of the telescope channels use Al:LiF coatings for optimum reflectivity between approximately 1000 and 1187 Å, and the other two channels use SiC coatings for optimized throughput between 905 and 1105 Å. The gratings are holographically ruled to correct largely for astigmatism and to minimize scattered light. The microchannel plate detectors have KBr photocathodes and use photon counting to achieve good quantum efficiency with low background signal. The sensitivity is sufficient to examine reddened lines of sight within the Milky Way and also sufficient to use as active galactic nuclei and QSOs for absorption-line studies of both Milky Way and extragalactic gas clouds. This spectral region contains a number of key scientific diagnostics, including O VI, H I, D I, and the strong electronic transitions of H2 and HD.
To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid ...tic disorders.
Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks.
Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures.
Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.
Purpose To compare the late complications in the Ahmed Baerveldt Comparison Study during 5 years of follow-up. Design Multicenter, prospective randomized clinical trial. Methods setting : Sixteen ...international clinical centers. study population : Two hundred seventy-six subjects aged 18-85 years with previous intraocular surgery or refractory glaucoma with intraocular pressure of >18 mm Hg. interventions : Ahmed Glaucoma Valve FP7 or Baerveldt Glaucoma Implant BG 101-350. main outcome measures : Late postoperative complications (beyond 3 months), reoperations for complications, and decreased vision from complications. Results Late complications developed in 56 subjects (46.8 ± 4.8 5-year cumulative % ± SE) in the Ahmed Glaucoma Valve group and 67 (56.3 ± 4.7 5-year cumulative % ± SE) in the Baerveldt Glaucoma Implant group ( P = .082). The cumulative rates of serious complications were 15.9% and 24.7% in the Ahmed Glaucoma Valve and Baerveldt Glaucoma Implant groups, respectively ( P = .034), although this was largely driven by subjects who had tube occlusions in the 2 groups (0.8% in the Ahmed Glaucoma Valve group and 5.7% in the Baerveldt Glaucoma Implant group, P = .037). Both groups had a relatively high incidence of persistent diplopia (12%) and corneal edema (20%), although half of the corneal edema cases were likely due to pre-existing causes other than the aqueous shunt. The incidence of tube erosion was 1% and 3% in the Ahmed Glaucoma Valve and Baerveldt Glaucoma Implant groups, respectively ( P = .04). Conclusions Long-term rates of vision-threatening complications and complications resulting in reoperation were higher in the Baerveldt Glaucoma Implant than in the Ahmed Glaucoma Valve group over 5 years of follow-up.
The authors report the CLASP (Edwards PASCAL Transcatheter Mitral Valve Repair System Study) expanded experience, 1-year outcomes, and analysis by functional mitral regurgitation (FMR) and ...degenerative mitral regurgitation (DMR).
The 30-day results from the CLASP study of the PASCAL transcatheter valve repair system for clinically significant mitral regurgitation (MR) have been previously reported.
Eligible patients had symptomatic MR ≥3+, were receiving optimal medical therapy, and were deemed candidates for transcatheter mitral repair by the local heart team. Primary endpoints included procedural success, clinical success, and major adverse event rate at 30 days. Follow-up was continued to 1 year.
One hundred nine patients were treated (67% FMR, 33% DMR); the mean age was 75.5 years, and 57% were in New York Heart Association functional class III or IV. At 30 days, there was 1 cardiovascular death (0.9%), MR ≤1+ was achieved in 80% of patients (77% FMR, 86% DMR) and MR ≤2+ in 96% (96% FMR, 97% DMR), 88% of patients were in New York Heart Association functional class I or II, 6-min walk distance had improved by 28 m, and Kansas City Cardiomyopathy Questionnaire score had improved by 16 points (p < 0.001 for all). At 1 year, Kaplan-Meier survival was 92% (89% FMR 96% DMR) with 88% freedom from heart failure hospitalization (80% FMR, 100% DMR), MR was ≤1+ in 82% of patients (79% FMR, 86% DMR) and ≤2+ in 100% of patients, 88% of patients were in New York Heart Association functional class I or II, and Kansas City Cardiomyopathy Questionnaire score had improved by 14 points (p < 0.001 for all).
The PASCAL transcatheter valve repair system demonstrated a low complication rate and high survival, with robust sustained MR reduction accompanied by significant improvements in functional status and quality of life at 1 year. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study CLASP; NCT03170349)
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Sarcomatoid features (SF) in renal cell carcinoma (RCC) denote poor prognosis. Data for metastatic chromophobe RCC (ChRCC) with SF are limited. We studied clinical outcomes and genomic features in ...this setting.
We performed a retrospective review of newly diagnosed metastatic ChRCC patients; end points included overall survival (OS), time to treatment failure (TTF), and time to metastatic recurrence (TTR) after nephrectomy for localized disease. A subset of patients underwent next-generation sequencing (NGS). Outcomes were compared using nonparametric tests.
One hundred nine patients with metastatic ChRCC were identified including 29 with SF. Median TTR after nephrectomy was shorter for patients with versus without SF (2.7 months 95% confidence interval (CI), 0.7-6.9 versus 48.8 months 95% CI, 30.8-80.7, log rank P < .001). Median TTF during first-line therapy was shorter for patients with versus without SF (1.8 months 95% CI, 0.9-2.7 vs. 8.0 months 95% CI, 5.1-13.0; log rank P < .001). No responses were observed in 6 patients treated with nivolumab including 4 with SF. Median OS was inferior for patients with versus without SF (38 months vs.7.5 months; hazard ratio, 4.7 95% CI, 2.7-8.2; P < .001). NGS, performed in 22 patients, showed that 64% and 45% harbored tumor protein P53 and phosphatase and tensin homolog alterations, respectively. Microsatellite instability high status was identified in 3 patients.
Metastatic ChRCC patients with SF had worse outcomes compared with those without SF. Median TTR < 3 months for this subgroup supports close surveillance after nephrectomy for localized tumors. Lack of benefit with various systemic regimens warrants studying underlying biology and investigating novel agents.
We studied cancer-specifics outcomes of 109 patients with metastatic chromophobe renal cell carcinoma with and without sarcomatoid features. We found that patients with metastatic sarcomatoid chromophobe renal cell carcinoma had uniformly poor outcomes with a short time to recurrence with metastatic disease after nephrectomy, limited response to systemic therapy, and poor overall survival compared with those without sarcomatoid features.
Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory ...biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.
Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory.
LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 95% CI 1.16, 1.37, p<0.001), IL-1RA (1.23 1.13, 1.34, p<0.0001), IL-6 (1.25 1.14, 1.36, p<0.001) and TNF-α (1.14 1.04, 1.25, p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 1.18, 1.48, p<0.001) and IL-6 (1.34 1.21, 1.49, p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 1.04, 1.26, p = 0.005).
In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction.
Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent ...bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8+ cells. Recognition of the involvement of cysLTs in the immunopathogenesis of various types of acute and chronic inflammatory disorders, especially bronchial asthma, prompted the development of selective cysLT receptor-1 (cysLTR1) antagonists, specifically montelukast, pranlukast, and zafirlukast. More recently these agents have also been reported to possess secondary anti-inflammatory activities, distinct from cysLTR1 antagonism, which appear to be particularly effective in targeting neutrophils and monocytes/macrophages. Underlying mechanisms include interference with cyclic nucleotide phosphodiesterases, 5′-lipoxygenase, and the proinflammatory transcription factor, nuclear factor kappa B. These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophils in vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies.
To prospectively determine whether early first-pass perfusion and delayed-enhancement magnetic resonance (MR) imaging sequences can enable differentiation of acute myocardial infarction (AMI) from ...myocarditis in patients with acute chest pain.
All examinations were performed according to guidelines of the institutional board on medical ethics and clinical investigation and after informed patient consent was obtained. Fifty-five patients with a clinical presentation suggestive but not typical of AMI were examined. At final diagnosis, 31 patients had AMI and 24 had myocarditis. At-rest MR imaging was performed and included first-pass perfusion and delayed-enhancement sequences. Three independent observers read each image data set separately and then in consensus. The main abnormalities included first-pass perfusion defects and delayed highly enhancing areas. The numbers and distributions of involved segments and the transmural extents and the shapes of the highly enhancing areas were noted. For comparisons between the AMI and myocarditis patient groups, the chi2 test was used to assess the locations of the abnormalities and the Mann-Whitney U test was used to assess the numbers of involved segments. The final diagnoses were obtained with coronary angiography as the reference standard for the AMI group and on the basis of normal coronary angiographic findings and the spontaneous resolution of clinical symptoms and wall motion abnormalities for the myocarditis group.
MR imaging patterns were significantly different between the two cardiac disease groups (P < .05). All the patients with AMI had a segmental early subendocardial defect, with corresponding segmental subendocardial or transmural delayed high enhancement in a predominantly anteroseptal or inferior vascular distribution in 28 patients. All patients with AMI had stenosis of at least the infarct-affected coronary artery. All but one of the patients with myocarditis had no early defect and focal or diffuse nonsegmental nonsubendocardial delayed enhancement predominantly in an inferolateral location.
Use of combined early- and late-perfusion MR imaging sequences helps to distinguish AMI from myocarditis.
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