MicroRNAs (miRs) have emerged as useful biomarkers for different disease states, including allergic inflammatory diseases such as asthma and eosinophilic esophagitis (EoE). Serum miRs are a possible non-invasive method for diagnosis of such diseases. We focused on microRNA-21 (miR-21) levels in serum, in order to assess the feasibility of using this gene as a non-invasive biomarker for these diseases in the clinic, as well as to better understand the expression pattern of miR-21 in allergic inflammation. We used quantitative PCR (QPCR) to assay miR-21 and other control miRs in esophageal biopsies from EoE patients and serum samples from EoE and asthma patients.Serum levels of miR-21 were significantly elevated in patients with asthma, whereas serum miR-21 levels were not associated with the presence of allergen-specific IgE (i.e. atopy). Esophageal biopsies showed a large elevation of miR-21 in EoE and an increase in miR-21 in EoE serum. Control U6 miR did not vary between asthma and control patients, however EoE serum had significantly decreased U6 microRNA compared to controls. The decreased U6 in EoE sera did not completely account for the relative increase in miR-21 in the sera of EoE patients. We report for the first time that miR-21 is elevated in the sera of both asthma and EoE patients. We find no relation between serum miR-21 levels and atopy. Our results thus suggest miR-21 is a novel biomarker for human allergic inflammatory diseases. Introduction:

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BACKGROUND Hemorrhage is the leading cause of preventable trauma‐related mortality and is frequently aggravated by acute traumatic coagulopathy (ATC). Viscoelastic tests such as rotational thromboelastometry (ROTEM) may improve identification and management of ATC. This study aimed to prospectively evaluate changes in ROTEM among combat casualties during the first 24 hours and compare the capabilities of our conventional clotting assay (international normalized ratio [INR], >1.2) to a proposed integrated ROTEM model (INR >1.2 with the addition of tissue factor pathway activation thromboelastometry [EXTEM] A5 ≤35 mm and/or EXTEM LI30 <97% on admission) to identify ATC and predict massive transfusion (MT). STUDY DESIGN AND METHODS This was a prospective observational study of trauma patients treated in NATO hospitals in Afghanistan between January 2012 and June 2013. ROTEM (EXTEM, functional fibrinogen thromboelastometry, APTEM, EXTEM with the addition of a fibrinolysis inhibitor) was performed on admission and at 6 and 24 hours by a designated research team. Treatment teams did not have access to the ROTEM results. RESULTS ROTEM values were available for 40 male casualties. The integrated ROTEM model classified 15% more patients with ATC than with INR alone and increased the detection of those that required MT by 22%. The sensitivity of the integrated ROTEM model to predict MT was higher than with INR greater than 1.2 (86% vs. 64%); however, specificity with both definitions for predicting MT was poor (38% vs. 50%, respectively). CONCLUSION These observations support the importance of early identification of and intervention in ATC. Integrating ROTEM into the definition of ATC would increase detection of those requiring MT arguing for its use as an adjunct to clinical presentation in the ultimate decision to initiate MT.

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OBJECTIVE: The engineered herpes simplex virus-1 G207, is a promising therapeutic option for central nervous system tumors. The first-ever pediatric phase 1 trial of continuous-infusion delivery of G207 via intratumoral catheters for recurrent or progressive malignant brain tumors is ongoing. In this article, we describe surgical techniques for the accurate placement of catheters in multiple supratentorial locations and perioperative complications associated with such procedures. METHODS: A prospective study of G207 in children with recurrent malignant supratentorial tumors is ongoing. Preoperative stereotactic protocol magnetic resonance imaging was performed, and catheter trajectories planned using StealthStation planning software. Children underwent placement of 3–4 silastic catheters using a small incision burr hole and the Vertek system. Patients had a preinfusion computed tomography scan to confirm correct placement of catheters. RESULTS: Six children underwent implantation of 3–4 catheters. Locations of catheter placement included frontal, temporal, parietal, and occipital lobes, and the insula and thalamus. There were no clinically significant perioperative complications. Postoperative computed tomography scans coupled with preoperative MRI scans demonstrated accurate placement of 21 of 22 catheters, with 1 misplaced catheter pulled back to an optimal location at the bedside. One patient had hemorrhage along the catheter tract that was clinically asymptomatic. Another patient had cerebrospinal fluid leak from a biopsy incision 9 days after surgery that was oversewn without complication. CONCLUSIONS: The placement of multiple intratumoral catheters in pediatric patients with supratentorial tumors via frameless stereotactic techniques is feasible and safe. Intratumoral catheters provide a potentially effective route for the delivery of G207 and may be employed in other trials utilizing oncolytic virotherapy for brain tumors.