Faculty Bibliography

Learning Objectives: The purpose of this study was to identify trends in postoperative transfusion practice in children undergoing cranial vault reconstruction. We hypothesize that young age is a risk factors for blood product transfusion requirement. Methods: A retrospective chart review was performed for all patients undergoing fronto-orbital advancement or cranial vault reconstruction at a single, medium-sized, academic tertiary pediatric hospital from June 14, 2011 to June 4, 2014. Diagnosis, procedure type, age, postoperative transfusion, hemoglobin level, platelet count, and international normalized ratio (INR) were recorded. Results: 90 patients were included in the analysis. Patient's age in months (mo) and years (yrs) ranged from 2 mo to 16 yrs. 25 patients (28%) were transfused with packed red blood cells (pRBC) and 4 patients (4%) were transfused with fresh frozen plasma (FFP). Median age of the total population was 0.8 yrs. Median age of patients receiving pRBC, FFP, and no transfusions were 0.7, 0.9, and 0.8 yrs, respectively. There may have been a trend toward younger age in patients that received pRBC transfusion when compared to patients receiving no transfusion (median 0.7 vs 0.8, p = 0.12, Wilcoxon rank-sum test). The hemoglobin nadir was 5.2 g/dL and 6 g/dL for patients who were transfused and who were not transfused with pRBCs, respectively. The mean hemoglobin level indicating need for pRBC transfusion was 6.85 + 1.07 g/dL and the mean INR indicating need for FFP transfusion was 1.38 + 0.05. Conclusions: This observational study of pediatric patients undergoing cranial vault reconstruction shows a trend that patients receiving postoperative pRBC transfusions were younger than patients that were not transfused. Further studies are needed to assess what impact age, hemoglobin nadir, and receipt of transfusion in the postoperative period has on short- and long-term postoperative outcomes

Treprostinil is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension (PAH). It is commonly administered through a central venous catheter (CVC). Treprostinil is associated with the incidence of Gram-negative bacterial bloodstream infections (BSI), a susceptibility that has been associated with a diluent used for treprostinil. We report the case of a 14-year-old boy with idiopathic PAH on continuous intravenous treprostinil therapy who presented with fever and fatigue. A blood culture drawn from his CVC was positive for the rare Gram-negative organism Chryseomonas luteola. The patient made a complete recovery with antibacterial treatment. This is the only documented case of a C. luteola BSI in a PAH patient receiving continuous intravenous treprostinil. We recommend maintaining a high index of suspicion for both common and rare Gram-negative pathogens and the early administration of appropriate antibiotic therapy in this population. The use of an alternate diluent solution, such as Sterile Diluent for Flolan, further decreases the infection risk.

Cyclic AMP-response element-binding protein (CREB) is a transcription factor implicated in growth factor-dependent cell proliferation and survival, glucose homeostasis, spermatogenesis, circadian rhythms, and synaptic plasticity associated with memory. To study the phenotype of CREB overexpression in vivo, we generated CREB transgenic (TG) mice in which a myeloid specific hMRP8 promoter drives CREB expression. CREB TG mice developed spontaneous skin abscesses more frequently than wild type (WT) mice. To understand the role of CREB in myeloid function and innate immunity, chemokine expression in bone marrow derived macrophages (BMDMs) from CREB TG mice were compared with BMDMs from WT mice. Our results demonstrated decreased Keratinocyte-derived cytokine (KC) in CREB TG BMDMs but not TNFalpha protein production in response to lipid A (LPA). In addition, mRNA expression of KC and IL-1beta (Interleukin)-1beta was decreased in CREB TG BMDMs; however, there was no difference in the mRNA expression of TNFalpha, MCP-1, IL-6 and IL-12p40. The mRNA expression of IL-1RA and IL-10 was decreased in response to LPA. Nuclear factor kappa B (NFkappaB) expression and a subset of its target genes were upregulated in CREB TG mouse BMDMs. Although neutrophil migration was the same in both CREB TG and WT mice, Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was significantly increased in neutrophils from CREB TG mice. Taken together, CREB overexpression in myeloid cells results in increased abscess formation in vivo and aberrant cytokine and chemokine response, and neutrophil function in vitro.

CREB is a transcription factor that regulates diverse cellular responses, including proliferation, survival, and differentiation. CREB is induced by a variety of growth factors and inflammatory signals and subsequently mediates the transcription of genes containing a cAMP-responsive element. Several immune-related genes possess this cAMP-responsive element, including IL-2, IL-6, IL-10, and TNF-alpha. In addition, phosphorylated CREB has been proposed to directly inhibit NF-kappaB activation by blocking the binding of CREB binding protein to the NF-kappaB complex, thereby limiting proinflammatory responses. CREB also induces an antiapoptotic survival signal in monocytes and macrophages. In T and B cells, CREB activation promotes proliferation and survival and differentially regulates Th1, Th2, and Th17 responses. Finally, CREB activation is required for the generation and maintenance of regulatory T cells. This review summarizes current advances involving CREB in immune function--a role that is continually being defined.