Development of a biomarker mortality risk model in acute respiratory distress syndrome

Background: There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome. Methods: This is a secondary analysis using a cohort of 252 mechanically ventilated subjects with the diagnosis of acute respiratory distress syndrome. Survival to day 7 with both day 0 (first day of presentation) and day 7 sample availability was required. Blood was collected for biomarker measurements at first presentation to the intensive care unit and on the seventh day. Biomarkers included cytokine-chemokines, dual-functioning cytozymes, and vascular injury markers. Logistic regression, latent class analysis, and classification and regression tree analysis were used to identify the plasma biomarkers most predictive of 28-day ARDS mortality. Results: From eight biologically relevant biomarker candidates, six demonstrated an enhanced capacity to predict mortality at day 0. Latent-class analysis identified two biomarker-based phenotypes. Phenotype A exhibited significantly higher plasma levels of angiopoietin-2, macrophage migration inhibitory factor, interleukin-8, interleukin-1 receptor antagonist, interleukin-6, and extracellular nicotinamide phosphoribosyltransferase (eNAMPT) compared to phenotype B. Mortality at 28 days was significantly higher for phenotype A compared to phenotype B (32% vs 19%, p = 0.04). Conclusions: An adult biomarker-based risk model reliably identifies ARDS subjects at risk of death within 28 days of hospitalization.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

February 2015 Tucson pulmonary journal club: fibrinolysis for PE

No abstract available. Article truncated at 150 words. The role of fibrinolytic therapy among patients with intermediate-risk pulmonary embo-lism (PE) is controversial (1). When right ventricular dysfunction and myocardial injury are associated with PE, there is an increased risk of adverse events (2). However, the risk of bleeding with fibrinolytic therapy has previously been thought to outweigh the benefits among patients without overt hemodynamic collapse. The Pulmonary Embolism Thrombolysis (PEITHO) trial was a multi-center, double-blind, placebo-controlled randomized trial designed to investigate the efficacy and safety of single-bolus injection with tenecteplase plus heparin anticoagulation versus heparin anticoagulation alone among normotensive patients with intermediate risk PE (3). The study included 1005 adult patients who were randomized within fifteen days of symptom onset; randomization occurred when both right ventricular dysfunction (echocardiography or spiral computed tomography) and myocardial injury (troponin I or T) were present. All patients were followed for 30 days. The primary outcome was death or hemo-dynamic collapse within 7 ..

Tucson critical care journal club: albumin use in the critical care unit

No abstract available. Article truncated at 150 words. Lyu PF, Hockenberry JM, Gaydos LM, Howard DH, Buchman TG, Murphy DJ. Impact of a sequential intervention on albumin utilization in critical care. Crit Care Med. 2016 Jul;44(7):1307-13. Albumin use for volume resuscitation in critically ill patients has been a hotly contested topic for decades (1). Widespread use of this expensive medicine in some settings has been based on perceived benefits without strong supporting evidence (2 ). Providing patient centered, evidence based, high value care is an expectation of most healthcare entities thus leading many hospitals to consider the cost effectiveness of their practices (3). One area of interest involves the use of albumin for volume resuscitation. Provider education has not changed practice; therefore, novel approaches to align provider behavior with evidence-based standards are necessary (4-6). In this pre-post quasi-experimental study with historical controls, investigators at Emory Critical Care Center (ECCC) hypnotized that a sequentially implemented multifaceted intervention would reduce ..

Medical image of the week: secondary pneumonia presenting as hemoptysis

No abstract available. Article truncated at 150 words. A 44 year-old man with a history of asthma presented to the hospital with encephalopathy, severe hypoxia and what was reported to be hematemesis. The patient was intubated in the Emergency Department and mechanical ventilation was instituted. Upper endoscopy was performed but source of bleeding could not be identified. Imaging of the chest showed pulmonary consolidation on both plain radiograph (D) and computed tomography (A-C). Bronchoscopy revealed a very friable mucosa with sloughing of the respiratory epithelium from the main carina (F) to at least the subsegmental level. Bronchoalveolar lavage (BAL) returned bloody fluid (E) but without any increase in blood with subsequent aliquots of fluid. The patient had progressively worsening hypoxia consistent with the acute respiratory distress syndrome (ARDS) requiring rescue maneuvers including paralysis, airway pressure release ventilation, and inhaled nitric oxide but we were unable to implement proning or transfer for extracorporeal life support due to profound cardiovascular ..

April 2014 Tucson critical care journal club: early goal-directed therapy

No abstract available. Article truncated at 150 words. In 2001, Early Goal Directed Therapy (EGDT) was demonstrated to improve 60 day mortality as compared to usual care practices, 44.3% vs. 56.9%, respectively (p=0.03) (1). EGDT and its components have since been incorporated into the major guidelines for the treatment of sepsis (2,3). The subsequent critical care literature has focused on adherence to EGDT protocols, the value of individual protocol components, and alternative protocols that are less standardized (4-6). The ProCESS trial was conducted to assess the continued benefit of protocol-based sepsis treatment strategies in a contemporary setting. ProCESS randomized 1351 adult patients who were suspected to have septic shock (≥2 SIRS criteria plus refractory hypotension and/or elevated lactate) to the original EGDT protocol, a newer simplified protocol, or usual care. The study took place in 31 academic centers in the United States; these centers could not have been previously using septic shock treatment protocols. The simplified protocol differed ..

September 2015 Tucson pulmonary journal club: genomic classifier for lung cancer

No abstract available. Article truncated at 150 words. Silvestri GA, Vachani A, Whitney D, et al. A bronchial genomic classifier for the diagnostic evaluation of lung cancer. N Engl J Med. 2015;373(3):243-51. Pulmonary lesions are a common diagnostic dilemma for clinicians. Current literature describes the sensitivity of bronchoscopic techniques to be between 34 and 88%; which varies significantly depending on size and location of the biopsied lesion (1). Previously described gene expression patterns have been found to be associated with malignancy in healthy epithelial cells of the proximal airways\(2). The primary aim of this study was to prospectively validate a specific gene expression classifier in patients undergoing bronchoscopic biopsy for suspected lung cancer. The study involved two independent, prospective, multicenter, observational studies (AEGIS-1 and AEGIS-2) conducted in the U.S., Canada and Ireland at 28 sites. Patients were excluded if they were never smokers, under age 21, or current cancer or former lung cancer patients. Patients were followed for ..

Inhaler device preferences in older adults with chronic lung disease

Introduction: Patient preferences are important for medication adherence and patient satisfaction, but little is known about older adult preferences for inhaler devices. Methods: We developed a 25-item written self-administered questionnaire assessing experience with inhalers, prior inhaler education, and preferences with respect to inhaler device features and inhaler device teaching. We then conducted a cross-sectional survey of patients at least 65 years of age with chronic lung disease who had experience using inhaler devices for at least six months in the ambulatory setting. Results: Fifty participants completed the questionnaire. The majority of participants (80%) reported prior experience with a metered dose inhaler (MDI), but only 26% used an MDI with a spacer. Most patients (76%) had received formal instruction regarding proper use of the inhaler, but only 34% had ever been asked to demonstrate their inhaler technique. Physician recommendation for an inhaler, cost of the inhaler device, and inhaler features related to convenience were important with respect to patient preferences. With regard to inhaler education, participants prefer verbal instruction and/or hands-on demonstration at the time a new inhaler is prescribed in the setting of the prescribing provider’s office. Conclusion: Patient preferences for inhaler devices and inhaler education among older adults indicate physician recommendation, cost, and convenience are important. The impact of patient preferences on inhaler adherence and clinical outcomes remains unknown