IntroductionAcute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI.MethodsWe performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection.ResultsModerate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.ConclusionsTwo novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.Trial registrationClinicalTrials.gov number NCT01209169.

Objectives: To determine which components of a residency Web site (RWS) are important to residency applicants. Methods: The authors performed a cross-sectional observational study of residency applicants. All applicants were invited to participate and were provided with a nine-question survey. Applicants were asked questions regarding the importance and impact of RWSs on the residency application process. They were also asked to rate items regarding content and aesthetics, and then rank all items in order of importance. Descriptive statistics are reported. Rank-order displays were determined using the Condorcet choice method. Results: One hundred eightyeight (82%) of the applicants responded to the survey. Seventy-eight percent of the respondents reported that information provided in an RWS influenced their decision to apply to a particular program (41% decided not to apply to at least one program based on the quality of its RWS). Applicants believed that presentation of the residency curriculum was most important. Information about the hospital and its affiliates, faculty and resident information, and research activities followed in the rank order. Least important to applicants were the aesthetic quality of the site, faculty/resident photographs, and educational resource materials. The authors report additional areas of content that applicants thought would be useful to view. Conclusions: The content, and not necessarily the aesthetic quality, of an RWS is important to residency applicants. The residency program Web site would seem to be an important factor in the applicant's decision to apply. The applicant's perspective provides training program directors and administrators with focused direction in Web site development or for upgrading existing RWSs for use by future applicants.

A biomarker panel of neutrophil gelatinase-associated lipocalin, interleukin-1ra, and Protein C was predictive of severe sepsis, septic shock, and death in ED patients with suspected sepsis. Further study is warranted to prospectively validate the clinical utility of these biomarkers and the sepsis score in risk-stratifying patients with suspected sepsis.

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Background-D-dimer has been reported to be elevated in acute aortic dissection. Potential use as a "rule-out" marker has been suggested, but concerns remain given that it is elevated in other acute chest diseases, including pulmonary embolism and ischemic heart disease. We evaluated the diagnostic performance of D-dimer testing in a study population of patients with suspected aortic dissection. Methods and Results-In this prospective multicenter study, 220 patients with initial suspicion of having acute aortic dissection were enrolled, of whom 87 were diagnosed with acute aortic dissection and 133 with other final diagnoses, including myocardial infarction, angina, pulmonary embolism, and other uncertain diagnoses. D-dimer was markedly elevated in patients with acute aortic dissection. Analysis according to control disease, type of dissection, and time course showed that the widely used cutoff level of 500 ng/mL for ruling out pulmonary embolism also can reliably rule out aortic dissection, with a negative likelihood ratio of 0.07 throughout the first 24 hours. Conclusion-D-dimer levels may be useful in risk stratifying patients with suspected aortic dissection to rule out aortic dissection if used within the first 24 hours after symptom onset.

Background The HEART score and North American Chest Pain Rule (NACPR) are decision rules designed to identify acute chest pain patients for early discharge without stress testing or cardiac imaging. This study compares the clinical utility of these decision rules combined with serial troponin determinations. Methods and Results A secondary analysis was conducted of 1005 participants in the Myeloperoxidase In the Diagnosis of Acute coronary syndromes Study (MIDAS). MIDAS is a prospective observational cohort of Emergency Department (ED) patients enrolled from 18 US sites with symptoms suggestive of acute coronary syndrome (ACS). The ability to identify participants for early discharge and the sensitivity for ACS at 30 days were compared among an unstructured assessment, NACPR, and HEART score, each combined with troponin measures at 0 and 3 hours. ACS, defined as cardiac death, acute myocardial infarction, or unstable angina, occurred in 22% of the cohort. The unstructured assessment identified 13.5% (95% CI 11.5-16%) of participants for early discharge with 98% (95% CI 95-99%) sensitivity for ACS. The NACPR identified 4.4% (95% CI 3-6%) for early discharge with 100% (95% CI 98-100%) sensitivity for ACS. The HEART score identified 20% (95% CI 18-23%) for early discharge with 99% (95% CI 97-100%) sensitivity for ACS. The HEART score had a net reclassification improvement of 10% (95% CI 8-12%) versus unstructured assessment and 19% (95% CI 17-21%) versus NACPR. Conclusions The HEART score with 0 and 3 hour serial troponin measures identifies a substantial number of patients for early discharge while maintaining high sensitivity for ACS.

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Ultrasound assistance was superior to LM techniques. D outperformed S but may require more training and personnel. All central cannula placement should be conducted with ultrasound assistance. The 2001 Agency for Healthcare Research and Quality Evidence Report dismissing static assistance was incorrect.