Rationale: Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality. Objectives: To determine whether intensive insulin therapy is associated with improved post-burn morbidity. Methods: A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n 5 60) or control (n 5 179). Measurements and Main Results: Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acutephase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P , 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P , 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P , 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P , 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P 5 0.14). Conclusions: In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309).
In vitro replicas of bone marrow can potentially provide a continuous source of blood cells for transplantation and serve as a laboratory model to examine human immune system dysfunctions and drug toxicology. Here we report the development of an in vitro artificial bone marrow based on a 3D scaffold with inverted colloidal crystal (ICC) geometry mimicking the structural topology of actual bone marrow matrix. To facilitate adhesion of cells, scaffolds were coated with a layer of transparent nanocomposite. After seeding with hematopoietic stem cells (HSCs), ICC scaffolds were capable of supporting expansion of CD34+ HSCs with B-lymphocyte differentiation. Three-dimensional organization was shown to be critical for production of B cells and antigen specific-antibodies. Functionality of bone marrow constructs was confirmed by implantation of matrices containing human CD34+ cells onto the backs of severe combined immunodeficiency (SCID) mice with subsequent generation of human immune cells.
The inability to produce perfusable microvasculature networks capable of supporting tissue survival and of withstanding physiological pressures without leakage is a fundamental problem facing the field of tissue engineering. Microvasculature is critically important for production of bioengineered lung (BEL), which requires systemic circulation to support tissue survival and coordination of circulatory and respiratory systems to ensure proper gas exchange. To advance our understanding of vascularization after bioengineered organ transplantation, we produced and transplanted BEL without creation of a pulmonary artery anastomosis in a porcine model. A single pneumonectomy, performed 1 month before BEL implantation, provided the source of autologous cells used to bioengineer the organ on an acellular lung scaffold. During 30 days of bioreactor culture, we facilitated systemic vessel development using growth factor-loaded microparticles. We evaluated recipient survival, autograft (BEL) vascular and parenchymal tissue development, graft rejection, and microbiome reestablishment in autografted animals 10 hours, 2 weeks, 1 month, and 2 months after transplant. BEL became well vascularized as early as 2 weeks after transplant, and formation of alveolar tissue was observed in all animals ( = 4). There was no indication of transplant rejection. BEL continued to develop after transplant and did not require addition of exogenous growth factors to drive cell proliferation or lung and vascular tissue development. The sterile BEL was seeded and colonized by the bacterial community of the native lung.
Objective Prolonged hospitalization due to burn injury results in physical inactivity and muscle weakness. However, how these changes are distributed among body parts is unknown. The aim of this study was to evaluate the degree of body composition changes in different anatomical regions during intensive care unit hospitalization (ICUh). Design Retrospective chart review. Setting Children’s burn hospital. Patients Twenty-four severely burned children admitted to our institution between 2000 and 2015. Interventions All patients underwent a dual-energy x-ray absorptiometry (DEXA) within 2 weeks after injury and 2 weeks before discharge to determine body composition changes. No subject underwent anabolic intervention. We analyzed changes of bone mineral content, bone mineral density, total fat mass, total mass, and total lean mass of the entire body and specifically analyzed the changes between the upper and lower limbs. Measurements and Main Results In the 24 patients, age was 10±5 years, total body surface area burned was 59±17%, time between DEXAs was 34±21 days, and length of stay was 39±24 days. We found a significant (p<0.001) average loss of 3% of lean mass in the whole body; this loss was significantly greater (p<0.001) in the upper extremities (17%) than in the lower extremities (7%). We also observed a remodeling of the fat compartments, with a significant whole-body increase in fat mass (p<0.001) that was greater in the truncal region (p<0.0001) and in the lower limbs (p<0.05). Conclusions ICUh is associated with greater lean mass loss in the upper limbs of burned children. Mobilization programs should include early mobilization of upper limbs to restore upper extremity function.
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