Six-month quality-of-life and functional status of acute respiratory distress syndrome survivors compared to patients at risk: a population-based study.

INTRODUCTION: The long-term attributable burden related to acute respiratory distress syndrome (ARDS) is not fully investigated. The aim of this study is to evaluate the quality of life (QOL) and functional status at 6 months after hospitalization in patients at risk for ARDS who did and did not develop the syndrome. METHOD: This is a population-based prospective cohort study of adult patients from Olmsted County, Minnesota, with or at risk for ARDS hospitalized from October 2008 to July 2011. The primary outcomes were changes in QOL and functional status, measured through 12-Item Short Form Survey (SF-12) and Barthel Index (BI) respectively, from baseline to 6 months, compared between survivors who did and did not develop ARDS. RESULTS: Of 410 patients with or at risk for ARDS, 98 had baseline surveys collected and 67 responded to a 6-month survey (26 ARDS, 41 non-ARDS). Both ARDS and non-ARDS groups had lower physical component of SF-12 at baseline compared to general population (P < 0.001 for both). ARDS patients had poorer baseline functional status compared to non-ARDS (mean BI 80 ± 25 vs. 88 ± 22, P = 0.03). No significant differences were observed for the change between 6 months and baseline BI (delta 2.3 for ARDS vs. 2.0 for non-ARDS, P = 0.5), or mental (delta 2.7 vs. 2.4, P = 0.9) or physical (delta -3 vs. -3.3, P = 0.9) component of SF-12 between survivors with and without ARDS. CONCLUSION: In this population-based study, decreased QOL and functional status 6 months after hospitalization were largely explained by baseline condition, with similar recovery in survivors who did and did not develop ARDS.

Neuromuscular and neuropsychological assessments in survivors of acute respiratory distress syndrome: exploratory comparisons with an at-risk cohort.

BACKGROUND: Long-term studies of survivors of acute respiratory distress syndrome (ARDS) have reported neuromuscular, quality of life, and neuropsychological impairments. This study aims to determine if development of ARDS was associated with neuromuscular weakness and depression at 6-month following hospital discharge in a population-based cohort of patients at high risk for ARDS. METHODS: A validated lung injury prediction model prospectively identified adult patients at increased risk for ARDS admitted to Mayo Clinic between October 2008 and July 2011. Instruments for functional impairment [Overall Neuropathy Limitations Scale (ONLS)] and the presence of depressive symptoms (the Yale Single Question) were administered at baseline and at 6 months. RESULTS: Of 107 patients enrolled in the study, 98 (92 %) underwent baseline assessment. Of these, 83 (85 %) were admitted to intensive care, 41 (42 %) developed ARDS, and 67 (68 %) completed assessment at 6 months. Patients with ARDS had longer intensive care and hospital length of stay (7.9 vs. 3.1 days, p = 0.005 and 19.5 vs. 10.6 days, p = 0.004, respectively). There was no difference in reported functional impairment at 6 months from baseline in the ARDS group compared to the non-ARDS group-mean ONLS Total Score 2.95 versus 2.07 p = 0.09 and 3.0 versus 2.1 p = 027, respectively. There was also no difference in the prevalence of depression at 6 months between the ARDS and non-ARDS group (21.9 vs. 30.7 % p = 0.41). CONCLUSIONS: In this single-center population-based cohort study, survivors of ARDS in the community had similar reported functional impairment and depression prevalence compared to an at-risk cohort that did not develop ARDS.

High leukocyte count is associated with peripheral vascular dysfunction in individuals with low cardiovascular risk.

BACKGROUND: Vascular dysfunction is a surrogate marker of early-stage atherosclerosis. Serum leukocyte count is a non-traditional risk factor of cardiovascular (CV) disease and has predictive value for CV outcome. The aim of this study was to investigate the relationship between leukocyte count and peripheral vascular dysfunction. METHODS AND RESULTS: In this cross-sectional study, 357 individuals without known CV disease and with low Framingham risk (10-year hard coronary heart disease risk <10%) were identified. Vascular function was measured by assessing reactive hyperemia-induced vasodilation (reactive hyperemia index, RHI). In 105 individuals with vascular dysfunction (29.4%), the median leukocyte count was significantly higher than in those with normal RHI (6.4 × 10(9)/L vs. 6.0 × 10(9)/L; P=0.04). The neutrophil count was the strongest predictor of impaired vascular function among leukocyte subtypes (odds ratio [OR], 2.70; 95% confidence interval [CI]: 1.58-4.60, P<0.001). In a multivariate logistic regression model, the highest quintile of neutrophil count (OR, 2.36; 95% CI: 1.35-4.12; P=0.003), body mass index (OR, 1.05; 95% CI: 1.01-1.09; P=0.009) and systolic blood pressure (OR, 0.97; 95% CI: 0.97-0.99; P<0.001) were independently predictive for vascular dysfunction. CONCLUSIONS: The highest quintile of leukocyte count is independently associated with vascular dysfunction in individuals with low CV risk. This suggests that subclinical inflammation affects vascular function. Leukocyte count may be useful for personalized risk stratification.

Novel functional risk factors for the prediction of cardiovascular events in vulnerable patients following acute coronary syndrome.

Over the years there has been considerable improvement in the clinical outcomes of patients treated for acute coronary syndrome (ACS). Despite a significant reduction in acute mortality, a large percentage of patients post ACS continue to experience adverse cardiovascular (CV) events, with high long-term mortality rates and overall suboptimal medical management. Long-term risk prediction tools rely on traditional CV risk factors and are developed and validated in specific populations. Established CV risk factors, however, only explain half or fewer of CV events. These risk models may thus not be optimal in determining individual risk for long-term adverse outcomes or in helping to identify individual patients who do not respond to therapy. Identifying the specific plaque characteristics associated with increased likelihood for thrombotic complications and rapid progression has led to the concept of the vulnerable plaque. Recently, "vulnerable myocardium" (ie, myocardium that is prone to myocardial ischemia and fatal arrhythmia) has been shown to play an important role in outcome. Both vulnerable plaque and vulnerable myocardium are associated with functional vascular abnormalities, such as endothelial dysfunction, which are considered a key event in the initiation, progression and complications of coronary artery disease. Endothelial dysfunction may serve as an underlying unifying mechanism that would independently predict long-term outcome in patients with ACS undergoing revascularization.

Normal vascular function as a prerequisite for the absence of coronary calcification in patients free of cardiovascular disease and diabetes.

BACKGROUND: The absence of coronary artery calcium (CAC) is a marker of very low cardiovascular risk. Endothelial cells may have an effect on the initiation and propagation of arterial calcification. We aimed to identify the relationship between the absence of CAC and endothelial function in individuals without cardiovascular disease and diabetes. METHODS AND RESULTS: CAC was assessed using electron-beam computed tomography and the calcium score was then computed. Endothelial function was measured by assessing reactive hyperemia-induced vasodilation and expressed by the reactive hyperemia index (RHI). Of 82 patients, 39 had non-detectable calcium (CAC score=0) and 43 had a CAC score >0. In the CAC score=0 group, the prevalence of normal endothelial function was 84.6%, compared to 48.8% in the CAC score >0 group, P=0.001. The absence of CAC was highly correlated with normal endothelial function (γ=0.704, P<0.001). On average, endothelial function was significantly better in the CAC score=0 group than in the CAC score >0 group (RHI 2.2±0.6 vs. 1.8±0.5, P=0.002). In a multivariate logistic regression model, only normal endothelial function (odds ratio [OR] 5.03, 95% confidence interval [CI] 1.55-16.27, P=0.007) and age (years) (OR 0.91, 95% CI 0.86-0.96, P=0.002) were independently associated with the absence of CAC. CONCLUSIONS: Normal functional status of the vasculature may be important for the prevention of coronary calcification and may partly account for the low cardiovascular risk of absent CAC.

Effects of statins on coronary and peripheral endothelial function in humans: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to quantify the effect of statins on peripheral and coronary endothelial function in patients with and without established cardiovascular disease. BACKGROUND: Early atherosclerosis is characterized by endothelial dysfunction, a known prognostic factor for cardiovascular disease. METHODS AND RESULTS: The search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 December 2009. Eligible studies were randomized controlled trials on the effects of statins compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Forty-six eligible trials enrolled a total of 2706 patients: 866 (32%) were women and 432 (16%) had established cardiovascular disease. Meta-analysis using random-effects models showed treatment with statins significantly improved endothelial function [standardized mean difference (SMD) 0.66, 95% CI 0.46-0.85, p < 0.001]. Subgroup analyses demonstrated statistically significant improvement in endothelial function assessed both peripherally by flow-mediated dilatation (SMD 0.68, 95% CI 0.46-0.90, p < 0.001) and venous occlusion plethysmography (SMD 0.59, 95% CI 0.06-1.13, p = 0.03) and centrally in the coronary circulation by infusion of acetylcholine (SMD 1.58, 95% CI 0.31-2.84, p = 0.01). Significant heterogeneity observed across studies was explained in part by the type of endothelial function measurement, statin type and dose, and study population differences. Exclusion of outlier studies did not significantly alter the results. CONCLUSION: Statin therapy is associated with significant improvement in both peripheral and coronary endothelial function. The current study supports a role for statin therapy in patients with endothelial dysfunction.

Encephalopathy of Unclear Etiology: A Diagnostic Dilemma.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially fatal condition caused by drug exposure resulting in hypersensitivity reaction with involvement of different organ systems. CASE PRESENTATION: We present a case of a 65-year-old man with a recent history of right total knee arthroplasty complicated by wound infection on a regimen of vancomycin who was transferred to our hospital for further management of fever, rigors, altered mental status, acute hypoxic respiratory failure, acute kidney injury, and development of an erythematous rash. DISCUSSION: DRESS syndrome was considered definite in this patient according to the European Registry of Severe Cutaneous Adverse Reaction Criteria, also known as RegiSCAR. To our knowledge, metabolic encephalopathy associated with multiorgan dysfunction resulting from vancomycin-induced DRESS syndrome has not been reported. CONCLUSION: A thorough analysis of recent medication history is essential for the prompt identification and management of this condition.

Towards the prevention of acute lung injury: a population based cohort study protocol.

BACKGROUND: Acute lung injury (ALI) is an example of a critical care syndrome with limited treatment options once the condition is fully established. Despite improved understanding of pathophysiology of ALI, the clinical impact has been limited to improvements in supportive treatment. On the other hand, little has been done on the prevention of ALI. Olmsted County, MN, geographically isolated from other urban areas offers the opportunity to study clinical pathogenesis of ALI in a search for potential prevention targets. METHODS/DESIGN: In this population-based observational cohort study, the investigators identify patients at high risk of ALI using the prediction model applied within the first six hours of hospital admission. Using a validated system-wide electronic surveillance, Olmsted County patients at risk are followed until ALI, death or hospital discharge. Detailed in-hospital (second hit) exposures and meaningful short and long term outcomes (quality-adjusted survival) are compared between ALI cases and high risk controls matched by age, gender and probability of developing ALI. Time sensitive biospecimens are collected for collaborative research studies. Nested case control comparison of 500 patients who developed ALI with 500 matched controls will provide an adequate power to determine significant differences in common hospital exposures and outcomes between the two groups. DISCUSSION: This population-based observational cohort study will identify patients at high risk early in the course of disease, the burden of ALI in the community, and the potential targets for future prevention trials.

Vascular reactivity to mental stress is associated with poor cardiovascular disease outcomes in females following acute coronary syndrome.

BACKGROUND: We aimed to test the hypothesis that peripheral endothelial dysfunction induced by mental stress may predict cardiovascular events after acute coronary syndrome beyond traditional cardiovascular disease risk factors. METHODS: This was a prospective study in which 417 patients who had acute coronary syndrome were enrolled in two sites at the US and Qatar. Cardiovascular disease risk factors such as past medical history, blood pressure, heart rate, peripheral endothelial dysfunction, and response to three different mental stress examinations (Stroop Color Word, Arithmetic, and Spiral Omnibus) as assessed by ratio of reactive hyperemia tonometry (EndoPAT) with stress over EndoPAT at rest were obtained at baseline. Major adverse cardiac events were then recorded at 1 year after the index event. RESULTS: There were no differences in baseline peripheral endothelial dysfunction or vascular response to mental stress between the US vs. Qatar patients. Women were more likely to experience major adverse cardiac events in the year following acute coronary syndrome (relative risk 2.42, 95% confidence interval 1.53-3.84, P = 0.044), and had a significantly lower mental stress ratio compared to women who did not (1.0 ± 0.17 vs. 1.20 ± 0.17, P = 0.04). In multivariate analyses stratified by sex, baseline peripheral endothelial dysfunction (EndoPAT < 1.7) (χ = 8.0, P = 0.005) and mental stress ratio (χ = 7.7, P = 0.006), were independently predictive of major adverse cardiac events in women, but not men. CONCLUSION: The current study demonstrates that in women both baseline endothelial function and vascular function in response to mental stress ratio are predictive of worse cardiovascular disease outcomes 1 year after acute coronary syndrome. The study may suggest an important mechanism for adverse clinical outcomes in women following acute coronary syndrome.

Endothelial function as a functional expression of cardiovascular risk factors.

Traditional cardiovascular risk (CV) factors based on the Framingham study have been used to estimate the risk of CV events and determine target cholesterol levels for primary prevention. Recently published systematic reviews have, however, demonstrated that the Framingham risk score is limited in certain cohorts and requires adjustment. Indeed, traditional CV risk factors fail to predict the development of coronary heart disease in 25-50% of cases. This underscores the complex interplay between traditional CV risk factors, genetic predisposition and other atheroprotective factors present in individuals of different populations in predicting CV events. Endothelial dysfunction, a functional expression of the inherent atherosclerotic risk representing an integrated index of both the overall CV risk-factor burden and the sum of all vasculoprotective factors in an individual, may serve as the missing link between CV risk factors and atherosclerotic disease. Endothelial function measurements may aid in future prediction of CV events and help identify high-risk patients for targeted therapy as well as provide a primary therapeutic end point for clinical follow-up of these patients. Recently introduced reactive hyperemia peripheral arterial tonometry is emerging as a promising tool in endothelial function measurement and CV risk stratification.

Long-term survival and quality of life after transfusion-associated pulmonary edema in critically ill medical patients.

BACKGROUND: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) commonly complicate transfusion in critically ill patients. Prior outcome studies of TACO and TRALI have focused on short-term morbidity and mortality, but the long-term survival and quality of life (QOL) of these patients remain unknown. METHODS: In a nested case-control study, we compared survival and QOL between critically ill medical patients who developed pulmonary edema after transfusion (TRALI or TACO) and medical critically ill transfused controls, matched by age, gender, and admission diagnostic group. QOL in survivors was assessed with a 36-item short form health survey 1 year after initial hospitalization. RESULTS: Hospital, 1-year, and 2-year mortality among the 74 TRALI cases and 74 matched controls were 43.2% vs 24.3% (P = .020), 63.8% vs 46.4% (P = .037) and 74.3% vs 54.3% (P = .031), whereas among the 51 TACO cases and 51 matched controls these values were 7.8% vs 11.8% (P = .727), 38.0% vs 28.0% (P = .371), and 44.9% vs 38.8% (P = .512). When adjusted for age and baseline severity of illness in a Cox proportional hazard analysis, the development of TRALI remained associated with decreased survival (hazard ratio 1.86; 95% CI, 1.19-2.93; P = .006). Both TRALI (P = .006, P = .03) and TACO (P = .03, P = .049) were associated with prolonged ICU and hospital lengths of stay. CONCLUSIONS: In critically ill medical patients, development of TRALI, but not TACO, is independently associated with decreased long-term survival.