Enoxaparin and antifactor Xa levels in pediatric acute burn patients.

Previous work from the authors' group showed a risk for inadequate enoxaparin dosing for venous thromboembolism prophylaxis in adult burn patients when traditional recommendations are used. The purpose of this study was to determine whether this also applied to pediatric burn patients. Included patients were acutely burned, aged 14 years or under, and admitted to the authors' regional burn center between October 1, 2004 and December 15, 2012. Thirty-five patients included in this analysis received enoxaparin for venous thromboembolism prophylaxis dosed initially at 0.5 mg/kg and monitored with anti-factor Xa levels (anti-Xa) between 0.2 and 0.4U/ml. Of the included patients, 80% were male with a median age of 8 years, a median TBSA of 16%, and a median length of stay of 23 days. Initially 21 patients (60%) had an undetectable anti-Xa (<0.2 U/ml). Enoxaparin doses were increased but 18 patients (51%) never achieved target anti-Xa. There were no significant differences in sex, weight, dose, depth of injury, or body mass index between those who received appropriate prophylaxis and those who were undertreated. However, median size of burn was significantly larger, median age and height were significantly lower in those who did not reach target. The low number of patients achieving target prophylactic anti-Xa in this study demonstrates the need for routine anti-Xa monitoring in pediatric burns. Additionally, pediatric patients with major burn injury may require initial dosing of enoxaparin greater than published recommendations because of altered pharmacokinetics.

Evaluation of an enoxaparin dosing calculator using burn size and weight.

Previous research has shown that inadequate antifactor Xa levels (anti-Xa) occur in burn patients and may increase the risk of venous thromboembolic events (VTE). The objective of this retrospective review was to investigate the usefulness of an enoxaparin dosing algorithm using a previously published equation. With institutional review board approval, all acute burn patients at an American Burn Association-verified regional burn center who were treated with enoxaparin for VTE prophylaxis and had at least one anti-Xa from May 1, 2011 to December 15, 2012 were included. Patients with subprophylactic anti-Xa received increased enoxaparin dose per unit protocol with the goal of obtaining a prophylactic anti-Xa (0.2-0.4 U/ml). Sixty-four patients were included in our analysis. The regression equation was used in 33 patients for initial enoxaparin dosing (Eq) whereas 31 patients received traditionally recommended prophylaxis dosing (No-Eq). Groups were comparable in sex, age, weight, inhalation injury, and burn size. Initial enoxaparin dosing in Eq was significantly more likely to reach target than in No-Eq (73 vs 32%; P = .002). No episodes of hemorrhage, thrombocytopenia, or heparin sensitivity were documented in either group. Median final enoxaparin dose required to reach prophylactic level was 40 mg every 12 hours (range, 30-80 mg). Twenty-one No-Eq patients ultimately reached target, and 11 of these final doses were equivalent to or greater than the predicted equation. Ten patients never reached prophylactic anti-Xa before enoxaparin was discontinued (nine from No-Eq). Two patients, one from each group, developed VTE complications despite appropriate anti-Xa for prophylaxis. A strong correlation was shown between weight, burn size, and enoxaparin dose (r = .68; P < .001). Use of the enoxaparin dosing algorithm significantly increased the frequency of obtaining a target initial anti-Xa. There were no bleeding complications. Enoxaparin dosing correlates to burn size and weight, making a standard dose inappropriate because patient habitus and extent of burn injury are highly variable. This simple equation improves enoxaparin dosing for acute adult burn patients.

Endometrial regenerative cells for treatment of heart failure: a new stem cell enters the clinic.

Heart failure is one of the key causes of morbidity and mortality world-wide. The recent findings that regeneration is possible in the heart have made stem cell therapeutics the Holy Grail of modern cardiovascular medicine. The success of cardiac regenerative therapies hinges on the combination of an effective allogeneic "off the shelf" cell product with a practical delivery system. In 2007 Medistem discovered the Endometrial Regenerative Cell (ERC), a new mesenchymal-like stem cell. Medistem and subsequently independent groups have demonstrated that ERC are superior to bone marrow mesenchymal stem cells (MSC), the most widely used stem cell source in development. ERC possess robust expansion capability (one donor can generate 20,000 patients doses), key growth factor production and high levels of angiogenic activity. ERC have been published in the peer reviewed literature to be significantly more effect at treating animal models of heart failure (Hida et al. Stem Cells 2008).Current methods of delivering stem cells into the heart suffer several limitations in addition to poor delivery efficiency. Surgical methods are highly invasive, and the classical catheter based techniques are limited by need for sophisticated cardiac mapping systems and risk of myocardial perforation. Medistem together with Dr. Amit Patel Director of Clinical Regenerative Medicine at University of Utah have developed a novel minimally invasive delivery method that has been demonstrated safe and effective for delivery of stem cells (Tuma et al. J Transl Med 2012). Medistem is evaluating the combination of ERC, together with our retrograde delivery procedure in a 60 heart failure patient, double blind, placebo controlled phase II trial. To date 17 patients have been dosed and preliminary analysis by the Data Safety Monitoring Board has allowed for trial continuation.The combined use of a novel "off the shelf" cell together with a minimally invasive 30 minute delivery method provides a potentially paradigm-shifting approach to cardiac regenerative therapy.

An evaluation of electrical stimulation for improving periprosthetic attachment.

Transcutaneous osseointegrated implants (TOI) have been shown to improve functionality for patients with limb loss by allowing direct skeletal attachment between an exoprosthesis and host bone. However, a lengthy rehabilitation period has limited the expansion of TOI and may be accelerated with electrical stimulation. The purpose of this study was to determine the ability of direct current (DC) cathode stimulation to enhance osseointegration of intramedullary implants in skeletally matured rabbits. Bilateral implants were inserted in the hind limbs of 25 adult female rabbits. The left hind limb of each animal was continually stimulated with a potential difference of 0.55 volts based on finite element analysis predictions. After sacrifice, the limbs were divided into two groups: Group I for histology and Group II for biomechanical testing. The bone-implant construct was evaluated in the Group I animals using appositional bone index (ABI), mineral apposition rates (MAR), histological staining, and scanning electron microscopy (SEM). Group II implants were sectioned and subjected to mechanical push-out tests. Data indicated no statistical differences for ABI, MAR, and porosity between the electrically stimulated implants (ESI) and the unstimulated control implants (UCI) at three weeks and six weeks. Higher mechanical push-out forces were observed in the UCI group at six weeks (p = 0.034). Data indicated that DC cathode stimulation may improve suboptimal implant "fit and fill" as an increase in trabecular bone was noted around the cathode in the ESI group. However, longer time duration animal studies and variations in electrical modalities may be required before electrically induced osseointegration becomes clinically feasible.

Clarifying the structure and bone mineral content of heterotopic ossification.

BACKGROUND: Heterotopic ossification (HO) has been reported as a pathologic process characterized by ectopic bone growth in muscle and/or periarticular regions. Previous reports have speculated that HO manifests as cancellous bone, cortical bone, or woven bone. Confusion regarding HO bone morphology has resulted from radiographic assessments and light microscopy, which lack the resolution required for accurately determining advanced bone architecture. Therefore, a more thorough histologic assessment using scanning electron microscopy (SEM) and backscatter electron (BSE) imaging was needed to improve HO characterization. MATERIALS AND METHODS: HO samples were collected from five adult trauma patients after surgical resection and examined with radiography, BSE, and histologic stains. RESULTS: BSE data demonstrated that HO was composed of a heterogeneous mixture of cortical and cancellous bone with distinct regions of fibrocartilage. Bone mineralization levels varied on a patient-specific basis, with the highest percentage of hypermineralization occurring in the oldest patient. BSE and histologic stains also indicated HO remodeling continued even after 3 y from injury to resection, as evident by osteoclastic resorption and osteoid deposition. CONCLUSIONS: BSE provided a more accurate understanding of HO bone mineralization and structure which may lead to improved surgical planning and treatment strategies for prevention of HO recurrence after resection.