Citations

Background— The residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Score is an objective measure of the degree and complexity of residual stenosis after percutaneous coronary intervention (PCI). Methods and Results— In the randomized PCI cohort of the SYNTAX Trial (n=903), the baseline and residual SYNTAX Scores were calculated. Subjects with a residual SYNTAX Score of 0 were defined as having undergone complete revascularization (CR), and a residual SYNTAX Score >0 as incomplete revascularization (ICR). Five-year clinical outcomes were stratified by CR and ICR (tertiles of the residual SYNTAX Score: >0–4, >4–8, and >8). In the PCI cohort, the mean baseline and residual SYNTAX Scores were 28.4±11.5 and 4.5±6.9, respectively. The mean Δ SYNTAX Score (representative of the burden of disease removed by PCI) was 23.8±10.9. The residual SYNTAX Score was distributed as follows: CR, 0 (n=386, 42.7%); ICR, >0 to 4 (n=184, 20.4%), >4 to 8 (n=167, 18.5%), >8 (n=153, 16.9%). A progressively higher residual SYNTAX Score was shown to be a surrogate marker of increasing clinical comorbidity and anatomic complexity. Subjects with CR or residual SYNTAX Scores ≤8 had comparable 5-year mortality (CR, 8.5%; residual SYNTAX Score >0–4, 8.7%; >4–8, 11.4%; P =0.60). A residual SYNTAX Score >8 was associated with 35.3% all-cause mortality at 5-years ( P <0.001). Stratified analyses in the predefined medical treated diabetic and left main subgroups yielded similar results. Conclusions— The residual SYNTAX Score was shown to be a powerful indicator of 5-year mortality in the SYNTAX Trial. The residual SYNTAX Score may aid in determining a reasonable level of revascularization. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00114972.

Obesity-metabolic disorders (ObM) often accompany renal artery stenosis (RAS). We hypothesized that the coexistence of ObM and RAS magnifies inflammation and microvascular remodeling in the stenotic kidney (STK) and aggravates renal scarring. Twenty-eight obesity-prone Ossabaw pigs were studied after 16 wk of a high-fat/high-fructose diet or standard chow including ObM-sham, ObM-RAS, Lean-RAS, or Lean-sham (normal control) groups. Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by multidetector computed tomography (CT), renal oxygenation and tubular transport capability by blood-oxygen-level-dependent MRI, and microcirculation by micro-CT for vessel density, and Western blotting for protein expressions of angiogenic factors (VEGF/FLK-1). Renal vein and inferior vena cava levels of inflammatory cytokines were measured to evaluate systemic and kidney inflammation. Macrophage (MØ) infiltration and subpopulations, fat deposition in the kidney, and inflammation in perirenal and abdominal fat were also examined. GFR and RBF were decreased in Lean-STK but relatively preserved in ObM-STK. However, ObM-STK showed impaired tubular transport function, suppressed microcirculation, and stimulated glomerulosclerosis. ObM diet interacted with RAS to blunt angiogenesis in the STK, facilitated the release of inflammatory cytokines, and led to greater oxidative stress than Lean-STK. The ObM diet also induced fat deposition in the kidney and infiltration of proinflammatory M1-MØ, as also in perirenal and abdominal fat. Coexistence of ObM and RAS amplifies renal inflammation, aggravates microvascular remodeling, and accelerates glomerulosclerosis. Increased adiposity and MØ-accentuated inflammation induced by an ObM diet may contribute to structural injury in the post-STK kidney.

AbstractBackgroundThe objective of our study was to understand the epidemiological and clinical features of respiratory adenoviral infections among children at a single institution over the course of several years.MethodsFrom January 2005 to April 2009, 1836 children (≤15 years old) who had been admitted to Korea University Ansan Hospital were tested for acute respiratory infection. The patients who were positive for an adenovirus infection were enrolled in this study, and their medical records were retrospectively reviewed.ResultsAdenoviruses were isolated from 310 patients. The male to female ratio was 1.6:1 and mean age was 32 ± 24 months. Children under 5 years of age had the highest prevalence. In 2007, adenovirus infections occurred endemically throughout the year. The clinical diagnoses were primarily upper respiratory tract infections (45.4%), lower respiratory tract infections (48.1%), and neurologic disease (5.2%). Associated symptoms, signs and laboratory findings included fever (91.9%), cough (83.9%), pharyngeal injection (62.3%), rale (32.6%) and elevated C‐reactive protein (93.9%). The most common radiologic findings were perihilar and peribronchial infiltrates (42.6%). Co‐infections were observed in 29 cases. The mean durations of hospitalization and fever were 6.2 ± 6.5 and 4.8 ± 3.1 days, respectively. The lengths of hospitalization were similar for patients admitted for upper respiratory tract infections with severe morbidity and those admitted for lower respiratory tract infections. No children in the study died.ConclusionOur study demonstrates that respiratory adenovirus infections are an important cause of hospitalization in young children, and contribute to a significant morbidity.

In order to develop novel, effective therapies for central nervous system regeneration, it is essential to better understand the role of neurotrophic factors and to design, accordingly, better artificial scaffolds to support both neurite outgrowth and synapse formation. Both nerve growth factor and brain-derived neurotrophic factor are major factors in neural survival, development, synaptogenesis, and synaptic connectivity of primary cultured neurons. As a prime candidate coating material for such neural cultures, carbon nanotubes offer unique structural, mechanical, and electrical properties. In this study, carbon nanotubes coated glass-coverslips were used as the matrix of a primary neural culture system used to investigate the effects of carbon nanotubes on neurite outgrowth and nerve growth factor/brain-derived neurotrophic factor release and expression. For these purposes, we performed comparative analyses of primary cultured neurons on carbon nanotubes coated, non-coated, and Matrigel-coated coverslips. The morphological findings showed definite carbon nanotubes effects on the neurite outgrowths and synaptogenic figures in both cortical and hippocampal neurons when compared with the non-coated negative control. Although the carbon nanotubes did not change neurotrophin expression levels, it stimulated brain-derived neurotrophic factor release into the media from both types of neurons. Accordingly, we suggest a different mechanism of action between carbon nanotubes and Matrigel in relation to the specific neurotrophic factors. Since carbon nanotubes supply long-term extracellular molecular cues for the survival and neurite outgrowths of cultured neurons, the results from this study will contribute to an understanding of carbon nanotubes biological effects and provide new insight into their role in the secretion of neurotrophic factors.

Background: Medullary thyroid cancer, although most commonly sporadic, may be part of the multiple endocrine neoplasia type 2 (MEN2) syndromes, generally due to mutations in the RET proto-oncogene. The majority of these mutations are located in exons 10, 11, and 13–16. More rarely, mutations in other exons have been described. We report for the first time a family from the United States with a rare mutation involving exon 8 of the RET proto-oncogene, corresponding to a p.Gly533Cys substitution (G533C) leading to the development of MEN2A syndrome in several affected family members. This mutation had only been previously described in a large family in Brazil and in 7.75% of patients with apparently sporadic medullary thyroid cancer (MTC) in Greece. Methods: Given a strong index of suspicion, a genetic analysis to evaluate for uncommon mutations in the RET proto-oncogene identified the presence of the G533C missense mutation, despite initial negative screening for common mutations. We describe a family with a total of 47 individuals from five generations with multiple members affected with this mutation. Results: Our data suggest that in patients with this mutation, pheochromocytoma is more common than previously reported, and that in some cases this mutation may be associated with a more aggressive phenotype than initially described. Conclusions: MEN2A due to the G533C mutation in exon 8 may be more common and more aggressive than previously recognized. In patients with medullary thyroid cancer with negative screening for common mutations in the RET oncogene but a strong index of suspicion, DNA sequence analysis of less commonly involved exons should be considered.