Preliminary experience with the smooth muscle troponin-like protein, calponin, as a novel biomarker for diagnosing acute aortic dissection

Aims The early diagnosis of acute aortic dissection (AD) remains challenging. We sought to determine the utility of the troponin-like protein of smooth muscle, calponin, as a diagnostic biomarker of acute AD. Methods and results Immunoassays against calponin (acidic, basic, and neutral isoforms) were developed and the levels were compared in a convenience sample of 59 patients with radiographically proven AD [34 males, age 59+15 (SD) years] vs. 158 patients suspected of having AD at presentation (116 males, age 63+15 years) but whose final diagnosis was not AD. Basic calponin, which is the most specific and abundant in smooth muscle, and acidic calponin, respectively, showed greater than two-fold and three-fold elevations in patients with acute AD. Diagnostic performance as determined by receiver-operating characteristics curve analysis showed that both acidic and basic calponin have the potential to detect AD in the first 24 h [respective areas under the curve (AUCs) 0.63 and 0.58], with superior performance of basic calponin (when compared with acidic) in the initial 6 h (respective AUCs 0.63 and 0.67). Conclusion Circulating calponin levels were elevated in acute AD compared with controls. These biomarkers have the potential for use as an early diagnostic biomarker for acute AD. Keywords Aortic dissection ? Biomarke

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Introduction: Acute 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. Methods: We 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. Results: Moderate 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 0.72. 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. Conclusions: Two 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

Evaluating outcomes associated with a discharge action plan employing single-dose home use of ondansetron in patients with acute gastroenteritis

Elizabeth Haines1, Robert van Amerongen2, Robert Birkhahn1, Wendy Wen1, Theodore Gaeta11Department of Emergency Medicine, 2Pediatric Emergency Services, New York Methodist Hospital, Brooklyn, NY, USAAbstract: Acute gastroenteritis accounts for 1–2 million annual pediatric emergency department visits in the US. The current literature supports the use of antiemetics, such as ondansetron, in the emergency department, reporting improved oral rehydration, cessation of vomiting, and reduction in the need for intravenous rehydration. However, there remains concern that using these agents may “mask alternative diagnoses” and negatively impact patient care. We present a case series of 29 patients who received a pediatric emergency department discharge action plan which allowed for a dose of ondansetron to be dispensed by the clinician at the time of discharge. Patients were instructed to administer the ondansetron at home for treatment of ongoing nausea and vomiting any time after 6 hours from the time of emergency department discharge. These patients were followed up at 3–5 days following discharge to assess for outcomes. Implications of this discharge action plan and future directions are discussed.Keywords: gastroenteritis, ondansetron, discharge action pla