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Arch Dis Child 2004;89:374-377. doi: 10. 1136/adc.2002.021816 Aims: To identify attendance patterns in a childhood cancer long term follow up clinic, in order to inform decision making strategies for efficient, [...]

Results demonstrate for the first time that the J-domain of the heat shock protein 70 DnaJ couples ATP hydrolysis to peptide capture as indicated by DnaK conformational change leading to the closure of the peptide-bonding domain. Data show that under the conditions of the J-domain binding to the ATPase domain, the J-domain accelerates ATP hydrolysis and simultaneous DnaK conformational change leading to peptide capture.

Benjamin D Horne,1,2 Rehan Ali,3 Dawn Midwinter,3 Catherine Scott-Wilson,4 Courtney Crim,4 Bruce E Miller,5 David B Rubin4 1Intermountain Medical Center Heart Institute, Salt Lake City, UT, USA; 2Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA; 3GlaxoSmithKline Plc., Uxbridge, UK; 4GlaxoSmithKline Plc., Research Triangle Park, Raleigh, NC, USA; 5GlaxoSmithKline Plc., Collegeville, PA, USACorrespondence: Benjamin D HorneIntermountain Medical Center Heart Institute, 5121 S Cottonwood Street, Salt Lake City, UT 84107, USAEmail benjamin.horne@imail.orgIntroduction: The presence of cardiovascular (CV) risk factors and CV disease in patients with chronic obstructive pulmonary disease (COPD) leads to worse outcomes. A number of tools are currently available to stratify the risk of adverse outcomes in these patients with COPD. This post hoc analysis evaluated the Summit Lab Score for validation as a predictor of the first episode of moderate-to-severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and other outcomes, in patients with COPD and high arterial pulse wave velocity (aPWV).Methods: Data from a multicenter, randomized, placebo-controlled, double-blind study were retrospectively analyzed to evaluate treatment effects of once-daily fluticasone furoate/vilanterol 100/25 μg in patients with COPD and an elevated CV risk (aPWV≥ 11m/s) over 24 weeks. The previously derived Summit Lab Score and, secondarily, the Intermountain Risk Score (IMRS) were computed for each patient, with patients then stratified into tertiles for each score. Risk of moderate-to-severe AECOPD was analyzed across tertiles using Kaplan–Meier survival curve and Cox regression analyses.Results: In 430 patients with COPD, Kaplan–Meier probabilities of no moderate-to-severe AECOPD for Summit Lab Score tertiles 1, 2, and 3 were 92.3%, 95.5%, and 85.1%, respectively (P trend = 0.015), over 24 weeks. Grouped by IMRS tertiles, the respective probabilities were 92.9%, 91.2%, and 88.3%, respectively (P trend = 0.141). Length of stay in the hospital (P = 0.034) and the hospital ward (P = 0.042) were also significantly different between Summit Lab Score tertiles but not for intensive care (P = 0.191).Conclusion: The Summit Lab Score was associated with the 24-week risk of moderate-to-severe AECOPD in COPD patients with elevated CV risk. Secondarily, IMRS showed a trend towards differences in the risk of AECOPD, which was not statistically significant.Keywords: chronic obstructive pulmonary disease (COPD), risk assessment, cardiovascular (CV) risk, arterial stiffness, Summit Lab Score, Intermountain Risk Score (IMRS)

Prior reports have suggested that an improved left ventricular (LV) function on LV assist device (LVAD) support might contribute to the development of device thrombosis. We investigated in a large multicenter dataset the association of LV function after LVAD with device thrombosis, cerebrovascular accident or transient ischemic attack (CVA/TIA), and hemolysis. The INTERMACS data were obtained via the NHLBI. We excluded patients with pulsatile-flow LVADs, right VAD only, total artificial heart, congenital heart disease, hypertrophic or restrictive cardiomyopathy, prior LVAD or heart transplantation, and baseline LV ejection fraction (LVEF) ≥40%. Patients were stratified by maximum LVEF after at least six months on LVAD support: <20%, 20-29%, 30-39%, 40-49%, and ≥50%. We assessed device thrombosis, CVA/TIA, and hemolysis rates across LVEF categories. Our study cohort comprised 9,556 patients. Baseline clinical characteristics are presented in the Table. Twelve percent of patients (n=1,136) achieved a post-LVAD LVEF higher than 40%. Patients in the post-LVAD LVEF ≥50%, 40-49%, 30-39% categories had a lower risk of developing device thrombosis compared to patients in the <20% LVEF group (adjusted hazard ratios [aHRs]: 0.75, 0.58, 0.83, respectively; p<0.05), while patients in the 20-29% group had a similar risk (aHR: 0.88; p=0.06). Overall, patients with post-LVAD LVEF ≥40% vs <40% had a lower risk of developing device thrombosis (aHR: 0.72; p<0.001). The risk of developing CVA/TIA was comparable across post-LVAD LVEF categories, while the risk of developing hemolysis was lower in patients comprising the 30-39% and 40-49% post-LVAD LVEF categories when compared to patients in the <20% post-LVAD LVEF group (aHRs: 0.81 and 0.72, respectively; p<0.001). Our findings from a large multicenter patient cohort indicate that an improved LV function on LVAD support is associated with a lower risk of device thrombosis. [ABSTRACT FROM AUTHOR]

Matthew J Hegewald,1,2 Benjamin D Horne,3,4 Frank Trudo,5 James L Kreindler,5 Yen Chung,5 Susan Rea,6 Denitza P Blagev1,2 1Pulmonary and Critical Care Medicine Division, Intermountain Medical Center, Murray, UT, USA; 2Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, UT, USA; 3Intermountain Heart Institute at Intermountain Healthcare, Salt Lake City, UT, USA; 4Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; 5Health Economics Outcomes Research, AstraZeneca, Wilmington, DE, USA; 6Enterprise Analytics, Intermountain Healthcare, Salt Lake City, UT, USACorrespondence: Matthew J HegewaldPulmonary and Critical Care Medicine Division, Intermountain Medical Center, 5121 S Cottonwood Street, Murray, UT 84107, USATel +1-801-507-4870Fax +1-801-507-4792Email matt.hegewald@imail.orgPurpose: This retrospective, observational cohort study investigated the association of blood eosinophil counts within 1 week of hospitalization for acute exacerbation of COPD (AECOPD) with subsequent risk of all-cause and COPD-related readmission from a large integrated health system.Patients and Methods: Electronic medical records were extracted for index hospitalization for AECOPD at all Intermountain Healthcare hospitals. The primary outcome was the relationship of blood eosinophil count to 30-day all-cause readmission; secondary outcomes were 60-day, 90-day, and 12-month all-cause readmission, COPD-related readmission, and empiric derivation of the eosinophil count with the highest area under the curve (AUC) for predicting 30-day all-cause readmission.Results: Of 2445 included patients, 1935 (79%) had a blood eosinophil count < 300 cells/μL and 510 (21%) had a count ≥ 300 cells/μL. Using a 300-cells/μL threshold, there was no significant difference between high and low eosinophil groups in 30-day (odds ratio [OR]=1.05, 95% confidence interval [CI]=0.75– 1.47) or 60-day (OR=1.15, 95% CI=0.88– 1.51) all-cause readmissions. However, patients with greater (versus lesser) eosinophil counts had increased 90-day and 12-month all-cause readmissions (OR=1.35, 95% CI=1.06– 1.72, and OR=1.32, 95% CI=1.07– 1.62). COPD-related readmission rates were significantly greater for patients with greater (versus lesser) eosinophil counts at 30, 60, and 90 days and 12 months (OR range=1.52– 1.97). A total of 70 cells/μL had the most discriminatory power to predict 30-day all-cause readmission (highest AUC).Conclusion: Eosinophil counts in patients with COPD were not associated with a difference in 30-day all-cause readmissions. However, greater eosinophil counts were associated with increased risk of all-cause readmission at 90 days and 12 months and COPD-related readmission at 30, 60, and 90 days and 12 months. Patients with eosinophils < 70 cells/μL had the lowest risk for 30-day all-cause readmission. Blood eosinophils in patients hospitalized with AECOPD may be a useful biomarker for the risk of hospital readmission.Keywords: AECOPD, phenotype, biomarkers, eosinophils, electronic medical records

Benjamin D Horne,1,2 Matthew J Hegewald,3 Courtney Crim,4 Susan Rea,5 Tami L Bair,1 Denitza P Blagev3 1Intermountain Medical Center Heart Institute, Salt Lake City, UT, USA; 2Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA; 3Division of Pulmonary Medicine, Department of Internal Medicine, Intermountain Medical Center, Salt Lake City, UT, USA; 4Research and Development, GlaxoSmithKline, Research Triangle Park, NC, USA; 5Care Transformation, Intermountain Healthcare, Salt Lake City, UT, USACorrespondence: Benjamin D HorneIntermountain Medical Center Heart Institute, 5121 S. Cottonwood Street, Salt Lake City, UT 84107, USATel +1801-507-4701Email benjamin.horne@imail.org Twitter@DrBenjaminHorneIntroduction: Tobacco use and other cardiovascular risk factors often accompany chronic obstructive pulmonary disease (COPD). This study derived and validated the Summit Score to predict mortality in people with COPD and cardiovascular risks.Methods: SUMMIT trial subjects (N=16,485) ages 40– 80 years with COPD were randomly assigned 50%/50% to derivation (N=8181) and internal validation (N=8304). Three external COPD validations from Intermountain Healthcare included outpatients with cardiovascular risks (N=9251), outpatients without cardiovascular risks (N=8551), and inpatients (N=26,170). Cox regression evaluated 40 predictors of all-cause mortality. SUMMIT treatments including combined fluticasone furoate (FF) 100μg/vilanterol 25μg (VI) were not included in the score.Results: Mortality predictors were FEV1, heart rate, systolic blood pressure, body mass index, age, smoking pack-years, prior COPD hospitalizations, myocardial infarction, heart failure, diabetes, anti-thrombotics, anti-arrhythmics, and xanthines. Combined in the Summit Score (derivation: c=0.668), quartile 4 vs 1 had HR=4.43 in SUMMIT validation (p< 0.001, 95% CI=3.27, 6.01, c=0.662) and HR=8.15 in Intermountain cardiovascular risk COPD outpatients (p< 0.001, 95% CI=5.86, 11.34, c=0.736), and strongly predicted mortality in the other Intermountain COPD populations. Among all SUMMIT subjects with scores 14– 19, FF 100μg/VI 25μg vs placebo had HR=0.76 (p=0.0158, 95% CI=0.61, 0.95), but FF 100μg/VI 25μg was not different from placebo for scores < 14 or > 19.Conclusion: In this post hoc analysis of SUMMIT trial data, the Summit Score was derived and validated in multiple Intermountain COPD populations. The score was used to identify a subpopulation in which mortality risk was lower for FF 100μg/VI 25μg treatment.Trial Registration: The SUMMIT trial is registered at ClinicalTrials.gov as number NCT01313676.Keywords: clinical decision tool, risk score, randomized controlled trial, Intermountain risk score, IMRS