This multicenter study suggests that proportion of patients extubated in the OR after heart operation is low. These data further suggest that extubation in the OR can be done successfully with a low complication rate.
Lung cancer continues to be the leading cause of cancer death worldwide. Recently, immunotherapy for non-small cell lung cancer (NSCLC) has emerged as a powerful treatment option for advanced lung cancer. The relative success of programmed death 1 (PD-1) and/or programmed death ligand 1 (PD-L1) antibodies in metastatic disease have increased interest in expanding their use to earlier stage NSCLC. The complex and diverse nature of stage III disease also invites the incorporation of immunotherapy into treatment plans in both the neoadjuvant and consolidation settings. Currently available data of anti-PD-(L)1 therapies in stage III NSCLC are limited. However, interim results from two studies are encouraging: a phase II neoadjuvant nivolumab trial demonstrated early signals of efficacy, and the phase III PACIFIC trial of durvalumab recently showed significant improvement in progression-free survival (PFS). Preliminary results for the phase II DETERRED trial of durvalumab have also been reported. Many studies are testing anti-PD-(L)1 therapies in the neoadjuvant and consolidation settings for stage III NSCLC, and will be discussed. As these studies mature they may provide further treatment options in management of stage III NSCLC.
Viral infections can alter the cellular epigenetic landscape, through modulation of either DNA methylation profiles or chromatin remodeling enzymes and histone modifications. These changes can act to promote viral replication or host defense. Herpes simplex virus type 1 (HSV-1) is a prominent human pathogen, which relies on interactions with host factors for efficient replication and spread. Nevertheless, the knowledge regarding its modulation of epigenetic factors remains limited. Here, we used fluorescently-labeled viruses in conjunction with immunoaffinity purification and mass spectrometry to study virus-virus and virus-host protein interactions during HSV-1 infection in primary human fibroblasts. We identified interactions among viral capsid and tegument proteins, detecting phosphorylation of the capsid protein VP26 at sites within its UL37-binding domain, and an acetylation within the major capsid protein VP5. Interestingly, we found a nuclear association between viral capsid proteins and the de novo DNA methyltransferase DNMT3A, which we confirmed by reciprocal isolations and microscopy. We show that drug-induced inhibition of DNA methyltransferase activity, as well as siRNA- and shRNA-mediated DNMT3A knockdowns trigger reductions in virus titers. Altogether, our results highlight a functional association of viral proteins with the mammalian DNA methyltransferase machinery, pointing to DNMT3A as a host factor required for effective HSV-1 infection.
Background-We hypothesized that children with dilated cardiomyopathy who require hospital admission are at increased risk for death or transplantation during their first hospitalization and in the first year that follows. We also assessed the value of routine data collected during that time to predict death or the need for transplantation prior to discharge and within 1 year of admission. Methods and Results-We conducted a retrospective review of 83 pediatric patients with dilated cardiomyopathy whose initial hospitalization fell between 2004 and 2009. The mean age at hospitalization was 7 years. The majority of patients demonstrated moderate or severe left ventricular dysfunction on initial echocardiogram (80%) and/or the need for intravenous inotropes within 7 days of hospital admission (69%). Five patients (6%) died, and 15 (18%) were transplanted in the initial hospitalization. At 1 year, 11/71 (15%) had died, and 27/71 (38%) were transplanted. The overall freedom from death, transplantation, or rehospitalization at 1 year following admission was 21%. Fractional shortening, left ventricular ejection fraction, serum cholesterol, uric acid, mixed venous saturation , and atrial filling pressures were all predictive of death or transplantation during the initial hospitalization. Left ventricular ejection fraction was predictive of death or transplantation at 1 year. Conclusions-The first hospitalization for dilated cardiomyopathy marks a period of high risk for clinical decline, end stage heart failure, and the need for cardiac transplantation. Echocardiographic function and hemodynamic and serum measurements may aid in predicting outcomes. Despite medical management, most patients will be rehospitalized and/or require cardiac transplantation within 1 year of admission. freedom from death or transplantation during the index hospitalization and at 1 year of follow-up. To our knowledge, this contemporary and homogenous cohort is the largest singleinstitution experience reported for hospitalized pediatric patients with DCM published to date. Methods Study Cohort and Data SourceWe identified and performed a retrospective chart review on 83 patients with DCM who had at least 1 hospitalization at Lucile Packard Children's Hospital at the time of, or subsequent to, their diagnosis between January 1, 2004, and December 31, 2009, of which 71 had reached the end point of death, transplantation, or had at least 1 year of follow-up. The diagnosis of DCM was based on the echocardiographic appearance of left ventricular dilatation and reduced left ventricular ejection fraction (LVEF), consistent with the approach taken in large pediatric registries. 3,7,8 Secondary diagnoses included DCM identified as primary idiopathic/familial or secondary to myocarditis, anthracycline toxicity, arrhythmias leading to heart failure, or genetic, neuromuscular, metabolic, or autoimmune disease. DCM was defined as idiopathic if no specific etiology of DCM was discovered and there were no affected family members. Myocarditis was either biopsy-p...
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