Faculty Bibliography

INTRODUCTION: Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease with a poor prognosis for which there is no effective medical therapy. An awareness of comorbidities that are treatable and might impact outcomes in these patients is therefore very important. We sought to determine the prevalence of coronary artery disease (CAD) in IPF patients in comparison to a control group of patients with chronic obstructive pulmonary disease (COPD). We also sought to assess the impact of CAD on IPF patient outcomes. PATIENTS AND METHODS: IPF and COPD transplant candidates whose work-up included left heart catheterization were categorized as having significant CAD, non-significant CAD or no disease. The risk factor profile and prevalence of CAD in both groups was compared. RESULTS: There were 73 IPF and 56 COPD patients. The prevalence of CAD was 65.8% in the IPF group compared to 46.1% in the COPD patients (p<0.028). Significant disease was present in 28.8% of IPF patients vs.16.1% of the COPD patients (p<0.081). Unsuspected significant CAD was found in 18% of IPF patients versus 10.9% of COPD patients (p<0.004). Outcomes of IPF patients with significant CAD was worse than those with no or non-significant disease (p<0.003) with a median survival of 572 days from the time of left heart catheterization. CONCLUSION: There is a higher prevalence of CAD in IPF patients compared to a similarly matched COPD group. This increased association appeared to be independent of common coronary artery risk factors. IPF patients with significant CAD appear to have worse outcomes.

PURPOSE: Introduction: IPF can be associated with a variety of comorbidities, including coronary artery disease (CAD). Significant CAD is associated with worse outcomes in IPF. Diagnosing and treating CAD at an early stage may improve mortality in IPF patients. We sought to determine the predictive ability of coronary calcification, assessed by HRCT scanning of the chest, for significant CAD. METHODS: We performed a retrospective review of IPF patients undergoing left heart catheterization (LHC) as part of their evaluation. Patients were categorized as having significant (>50% stenosis), mild (<50% stenosis), or no CAD based on LHC results. The most current available HRCT was assessed for the degree of coronary calcification. Calcification was graded as; 0-no visible calcification, 1-trace calcification, 2-mild calcification, 3-moderate calcification and 4-severe calcification. RESULTS: Sixty IPF patients qualified for the analysis. LHC demonstrated significant CAD in 26.6% (16/60) of the patients, while 41.6% (25/60) had mild disease and 31.6% (19/60) had no CAD. The median time interval between the LHC and the reviewed HRCT was 41 days. The sensitivity of grade 3 or 4 calcification for significant CAD was 75%, while the specificity was 82%. The sensitivity and specificity of grade 3 or 4 calcification for any CAD was 44% and 89%, respectively. CONCLUSION: HRCT is a useful screening tool for the detection of significant CAD in patients with IPF. In addition to parenchymal changes, HRCT degree of coronary calcification should routinely be assessed in patients with IPF. CLINICAL IMPLICATIONS: The early detection of CAD in IPF through routine HRCT may have implications for patient outcomes

PURPOSE: In our institution, the critical care admitting resident (CCAR) assesses unstable patients on the general wards. The assessment time and implementation of the appropriate intervention is crucial in patients' outcome. We reviewed whether the implementation of a standardized evaluation facilitated this process and effected survival. METHODS: The CCAR was required to complete a single page "assessment sheet" which included pertinent medical background, current clinical status, as well as a plan of therapy. The general goal was to have the assessment and discussion with the medical intensivist done within 20 minutes of receiving the consult. We then did a retrospective chart review with attention paid to the time of implementation of therapies, as well as their effect on patient mortality. Incomplete evaluations and those with do not resuscitate orders (DNR) were excluded from outcome data. RESULTS: 70 of 138 evaluations (51%) were done and discussed with the medical intensivist within 20 minutes, resulting in an overall survival rate of 88%. An additional 59 patients were evaluated in the 21-40 minute interval, resulting in a 92% survival rate. Overall, 129 patients (93%) were evaluated within 40 minutes, leading to an overall 90% survival rate. It was also observed that therapy implemented early by the primary team, (i.e. before the CCAR was called), led to 93% survival rate (64 of 69 patients). CONCLUSION: Implementation of therapy in a succinct manner to critically ill patients results in better outcome. By initiating an "assessment sheet," we have provided a more streamlined approach to evaluate critically ill patients for physicians in training. Secondly, we observed a significant improvement in survival when an intervention was made early; even prior to contacting the critical care team. CLINICAL IMPLICATIONS: Standardized evaluation of critically ill patients for residents in training will lead to faster implementation of therapy, which has been shown to improve outcome. Using this!

Polycomb group protein Ezh2, one of the key regulators of development in organisms from flies to mice, exerts its epigenetic function through regulation of histone methylation. Here, we report the existence of the cytosolic Ezh2-containing methyltransferase complex and tie the function of this complex to regulation of actin polymerization in various cell types. Genetic evidence supports the essential role of cytosolic Ezh2 in actin polymerization-dependent processes such as antigen receptor signaling in T cells and PDGF-induced dorsal circular ruffle formation in fibroblasts. Revealed function of Ezh2 points to a broader usage of lysine methylation in regulation of both nuclear and extra-nuclear signaling processes

Polycomb group protein Ezh2 is an essential epigenetic regulator of embryonic development in mice, but its role in the adult organism is unknown. High expression of Ezh2 in developing murine lymphocytes suggests Ezh2 involvement in lymphopoiesis. Using Cre-mediated conditional mutagenesis, we demonstrated a critical role for Ezh2 in early B cell development and rearrangement of the immunoglobulin heavy chain gene (Igh). We also revealed Ezh2 as a key regulator of histone H3 methylation in early B cell progenitors. Our data suggest Ezh2-dependent histone H3 methylation as a novel regulatory mechanism controlling Igh rearrangement during early murine B cell development.